Compositions and methods for precision cancer treatment

Abstract

Disclosed herein is a composition comprising one or more antineoplastons, and the use of the composition in the method for treating and / or preventing cancer, the method for prolonging the survival of an individual, and the method for preventing and / or reducing the metastasis of cancer.The method further comprises: obtaining a biological sample from an individual before and / or after administering a high-precision cancer treatment; subjecting the biological sample to cell-free DNA (cfDNA) analysis, comprising next-generation sequencing of one or more cancer-related genes, wherein the sequencing of one or more cancer-related genes comprises identifying one or more genomic abnormalities, including mutation, insertion, deletion, chromosome rearrangement, copy number abnormality, or any combination thereof; and then diagnosing the individual as needing high-precision cancer treatment.

Description

[Technical Field]

[0001] I. CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Patent Application No. 63 / 396,104, filed August 8, 2022, which is incorporated herein by reference in its entirety. [Background technology]

[0002] II. Background Cancer is intractable in terms of the breadth and scope of its diversity, spanning genetics, cell and tissue biology, pathology, and response to treatment. Ever more powerful experimental and computational tools and technologies are providing an avalanche of "big data" on the myriad manifestations of the disease it encompasses. The integrative concepts embodied in the hallmarks of cancer are helping to extract increasingly coherent science from this complexity, and the tentative new aspects presented in this Perspective may add value to efforts to more fully understand the mechanisms of cancer development and malignant progression and to apply these insights to cancer medicine.

[0003] Cancer is one of the leading causes of death worldwide. In 2018, there were 18.1 million new cases and 9.5 million cancer-related deaths worldwide. By 2040, the number of new cancer cases per year is expected to increase to 29.5 million, and the number of cancer-related deaths to 16.4 million. In general, cancer rates are highest in countries where the population has the highest life expectancy, education level, and standard of living. However, for some cancer types, such as cervical cancer, the opposite is true: incidence rates are highest in countries where the population ranks low on these measures. Summary of the Invention [Means for solving the problem]

[0004] Despite advances in medical management, there remains an unmet medical need for developing methods to provide precision cancer treatment to subjects with cancer (e.g., terminal cancer). [Brief explanation of the drawings]

[0005] [Figure 1]

[0001] Figure 1 shows Kaplan-Meier survival curves for all evaluable terminal cancer patients treated with or without AS therapy. [Figure 2]

[0002] Figure 2 shows Kaplan-Meier survival curves for evaluable, end-stage cancer patients treated with or without AS therapy, where the patients were diagnosed with head and neck, kidney, ovarian, pancreatic, or prostate cancer (e.g., common cancers excluding BE, CL, and LU). [Figure 3] Figure 3 shows Kaplan-Meier survival curves for evaluable terminal cancer patients treated with or without AS therapy. Here, patients were diagnosed with uncommon cancers. Patients with multiple diagnoses are listed only once. [Figure 4]

[0004] Figure 4 shows a variant allele frequency map of mutations detected by ctDNA in an individual patient diagnosed with ER+, PR-, HER-2+ invasive ductal carcinoma (stage IV) with liver metastasis who responded to AS treatment. Mutant genes PIK3CA and FGFR2 were no longer present as of November 1, 2017, due to successful treatment. [Figure 5-1]

[0005] Figure 5 shows a variant allele frequency map of mutations detected by ctDNA in an individual patient diagnosed with widespread DCIS, ER-, PR-, HER-2+ invasive ductal carcinoma (stage IV) with lymph node and skin metastases who responded to AS treatment. Mutated genes TP53, ERBB2, and SMAD4 were no longer present in the Guardant test results on September 13, 2018, and January 16, 2019, due to successful treatment. [Figure 5-2]Figure 5 shows the variant allele frequency map of mutations detected by ctDNA in an individual patient diagnosed with extensive DCIS, ER-, PR-, HER-2+ invasive ductal carcinoma (stage IV) with lymph node and skin metastases who responded to AS treatment. Mutated genes TP53, ERBB2, and SMAD4 were no longer present in the Guardant test results on September 13, 2018, and January 16, 2019, due to successful treatment.

[0006] [Figure 6] Figure 6 shows the variant allele frequency map of mutations detected by ctDNA in an individual patient diagnosed with ER+, PR+, HER-2- invasive ductal carcinoma (stage IV) with widespread bone metastases who responded to AS treatment. The mutated gene, PIK3CA, was no longer present on October 2, 2018, due to successful treatment.

[0007] [Figure 7-1] Figure 7 shows the variant allele frequency map of mutations detected by ctDNA in an individual patient diagnosed with ER+, PR+, HER-2- invasive ductal carcinoma (stage IV) with multiple metastases to lymph nodes, bone, and brain who responded to AS treatment. Mutant genes MYC, BRCA2, PIK3CA, APC, BRCA1, FGFR3, RAF1, and ARAF were no longer present by April 8, 2019, due to successful treatment. [Figure 7-2] Figure 7 shows the variant allele frequency map of mutations detected by ctDNA in an individual patient diagnosed with ER+, PR+, HER-2- invasive ductal carcinoma (stage IV) with multiple metastases to lymph nodes, bone, and brain who responded to AS treatment. Mutant genes MYC, BRCA2, PIK3CA, APC, BRCA1, FGFR3, RAF1, and ARAF were no longer present by April 8, 2019, due to successful treatment. [Figure 7-3]Figure 7 shows the variant allele frequency map of mutations detected by ctDNA in an individual patient diagnosed with ER+, PR+, HER-2- invasive ductal carcinoma (stage IV) with multiple metastases to lymph nodes, bone, and brain who responded to AS treatment. Mutant genes MYC, BRCA2, PIK3CA, APC, BRCA1, FGFR3, RAF1, and ARAF were no longer present by April 8, 2019, due to successful treatment.

[0008] [Figure 8-1] Figure 8 shows the variant allele frequency map of mutations detected by ctDNA in an individual patient diagnosed with ER+, PR-, HER-2+ infiltrating ductal carcinoma of the left breast (stage IV) with widespread metastases to the brain, bone, liver, and lung, and epidural involvement at T6-T12, who responded to AS treatment. Mutant genes EGFR, ERBB2, and PIK3CA were no longer present as of December 30, 2019, due to successful treatment. [Figure 8-2] Figure 8 shows the variant allele frequency map of mutations detected by ctDNA in an individual patient diagnosed with ER+, PR-, HER-2+ infiltrating ductal carcinoma of the left breast (stage IV) with widespread metastases to the brain, bone, liver, and lung, and epidural involvement at T6-T12, who responded to AS treatment. Mutant genes EGFR, ERBB2, and PIK3CA were no longer present as of December 30, 2019, due to successful treatment.

[0009] [Figure 9-1]Figure 9 shows a variant allele frequency map of mutations detected by ctDNA in an individual patient diagnosed with ER+, PR-, HER-2+ breast cancer with metastases to lymph nodes, brain, lung, pleura, bone, peritoneum, and ovaries who responded to AS treatment. Mutant genes CCND1, CDK6, ERBB2, FGFR1, PIK3CA, PTEN, ARID1A, and PDGFRA were no longer present on January 6, 2020, due to successful treatment. [Figure 9-2] Figure 9 shows a variant allele frequency map of mutations detected by ctDNA in an individual patient diagnosed with ER+, PR-, HER-2+ breast cancer with metastases to lymph nodes, brain, lung, pleura, bone, peritoneum, and ovaries who responded to AS treatment. Mutant genes CCND1, CDK6, ERBB2, FGFR1, PIK3CA, PTEN, ARID1A, and PDGFRA were no longer present on January 6, 2020, due to successful treatment. [Figure 9-3] Figure 9 shows a variant allele frequency map of mutations detected by ctDNA in an individual patient diagnosed with ER+, PR-, HER-2+ breast cancer with metastases to lymph nodes, brain, lung, pleura, bone, peritoneum, and ovaries who responded to AS treatment. Mutant genes CCND1, CDK6, ERBB2, FGFR1, PIK3CA, PTEN, ARID1A, and PDGFRA were no longer present on January 6, 2020, due to successful treatment.

[0010] [Figure 10-1] Figure 10 shows the variant allele frequency map of mutations detected by ctDNA in an individual patient diagnosed with high-grade invasive urothelial carcinoma of the bladder (stage IV) with metastases to lymph nodes, lungs, bones, and brain who responded to AS. Mutant genes EGFR were no longer present on November 5, 2019, BRAF was no longer present on April 16, 2020, and mutant TERT, TP53, and ERBB2 had decreased in concentration on April 16, 2020. [Figure 10-2]Figure 10 shows the variant allele frequency map of mutations detected by ctDNA in an individual patient diagnosed with high-grade invasive urothelial carcinoma of the bladder (stage IV) with metastases to lymph nodes, lungs, bones, and brain who responded to AS. Mutant genes EGFR were no longer present on November 5, 2019, BRAF was no longer present on April 16, 2020, and mutant TERT, TP53, and ERBB2 had decreased in concentration on April 16, 2020.

[0011] [Figure 11] FIG. 11 shows survival analysis of patients with common cancers treated with AS and A10 (ANP).

[0012] [Figure 12] FIG. 12 shows survival analysis of patients with uncommon cancers treated with AS and A10 (ANP). DETAILED DESCRIPTION OF THE INVENTION

[0013] IV.Overview Disclosed herein are compositions comprising one or more antineoplastons.

[0014] Disclosed herein are pharmaceutical formulations that include one or more antineoplastons and one or more pharmaceutically acceptable carriers.

[0015] Disclosed herein are methods of treating and / or preventing cancer, the methods comprising administering a precision cancer treatment to a subject in need thereof, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment.

[0016] Disclosed herein is a method of treating cancer, comprising obtaining a biological sample from a subject in need thereof; subjecting the biological sample to cell-free DNA (cfDNA) analysis; diagnosing the subject as in need of a precision cancer treatment if the expression and / or amount of one or more genomic aberrations in the biological sample is greater than the expression and / or amount of the same one or more genomic aberrations in a control sample; and administering the precision cancer treatment to the subject, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment.

[0017] Disclosed herein are methods of treating cancer, the method comprising obtaining a biological sample from a subject in need thereof; subjecting the biological sample to cell-free DNA (cfDNA) analysis; diagnosing the subject as in need of a precision cancer treatment if the expression and / or amount of one or more genomic aberrations in the biological sample is greater than the expression and / or amount of the same one or more genomic aberrations in a control sample; administering the precision cancer treatment to the subject; and measuring the subject's tumor response and / or the subject's molecular response.

[0018] Disclosed herein is a method of treating cancer, comprising obtaining a biological sample from a subject in need thereof; subjecting the biological sample to cell-free DNA (cfDNA) analysis, wherein the expression and / or amount of one or more genomic aberrations in the biological sample is greater than the expression and / or amount of the same one or more genomic aberrations in a control sample, diagnosing the subject as being in need of a precision cancer treatment; and administering the precision cancer treatment to the subject, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment.

[0019] Disclosed herein are methods for extending survival of a subject, the methods comprising administering a precision cancer treatment to a subject in need thereof, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment, and wherein the subject's life expectancy is extended.

[0020] Disclosed herein is a method for extending survival of a subject, the method comprising obtaining a biological sample from a subject in need thereof; subjecting the biological sample to cell-free DNA (cfDNA) analysis; diagnosing the subject as being in need of a precision cancer treatment if the expression and / or amount of one or more genomic aberrations in the biological sample is greater than the expression and / or amount of the same one or more genomic aberrations in a control sample; and administering the precision cancer treatment to the subject, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment and wherein the subject's life expectancy is extended.

[0021] Disclosed herein is a method for extending survival of a subject, the method comprising obtaining a biological sample from a subject in need thereof; subjecting the biological sample to cell-free DNA (cfDNA) analysis; diagnosing the subject as being in need of a precision cancer treatment if the expression and / or amount of one or more genomic aberrations in the biological sample is greater than the expression and / or amount of the same one or more genomic aberrations in a control sample; and administering the precision cancer treatment to the subject, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment and wherein the subject's life expectancy is extended.

[0022] Disclosed herein is a method for extending survival of a subject, the method comprising the steps of obtaining a biological sample from a subject in need thereof; subjecting the biological sample to cell-free DNA (cfDNA) analysis, wherein the expression and / or amount of one or more genomic aberrations in the biological sample is greater than the expression and / or amount of the same one or more genomic aberrations in a control sample, and diagnosing the subject as being in need of a precision cancer treatment; and administering the precision cancer treatment to the subject, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment and the subject's life expectancy is extended.

[0023] Disclosed herein are methods for preventing and / or reducing metastasis, comprising administering a precision cancer treatment to a subject in need thereof, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment, and wherein metastasis is prevented and / or reduced.

[0024] Disclosed herein is a method for preventing and / or reducing metastasis, comprising the steps of obtaining a biological sample from a subject in need thereof; subjecting the biological sample to cell-free DNA (cfDNA) analysis; diagnosing the subject as being in need of a precision cancer treatment if the expression and / or amount of one or more genomic aberrations in the biological sample is greater than the expression and / or amount of the same one or more genomic aberrations in a control sample; and administering the precision cancer treatment to the subject, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment and metastasis is prevented and / or reduced.

[0025] Disclosed herein is a method for preventing and / or reducing metastasis, comprising the steps of obtaining a biological sample from a subject in need thereof; subjecting the biological sample to cell-free DNA (cfDNA) analysis; diagnosing the subject as being in need of a precision cancer treatment if the expression and / or amount of one or more genomic aberrations in the biological sample is greater than the expression and / or amount of the same one or more genomic aberrations in a control sample; and administering the precision cancer treatment to the subject, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment and metastasis is prevented and / or reduced.

[0026] Disclosed herein is a method for preventing and / or reducing metastasis, comprising the steps of obtaining a biological sample from a subject in need thereof; subjecting the biological sample to cell-free DNA (cfDNA) analysis, wherein if the expression and / or amount of one or more genomic aberrations in the biological sample is greater than the expression and / or amount of the same one or more genomic aberrations in a control sample, diagnosing the subject as being in need of a precision cancer treatment; and administering the precision cancer treatment to the subject, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment and metastasis is prevented and / or reduced.

[0027] V. Detailed Description The present disclosure describes formulations, combination compositions, kits, capsules, containers, and / or methods related thereto. It should be understood that the inventive aspects of the present disclosure are not limited to a specific synthesis method unless otherwise specified, nor are they limited to a specific reagent unless otherwise specified, and therefore may of course vary. It is also understood that the terminology used herein is merely for the purpose of describing specific embodiments and is not intended to be limiting. Although any methods and materials similar or equivalent to those described herein can be used to practice or test the present invention, exemplary methods and materials are described here.

[0028] All publications mentioned herein are incorporated by reference to disclose and describe the methods and / or materials with which the cited publications pertain. The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein should be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention.

[0029] A.Definition Before the present compounds, compositions, articles, systems, devices, and / or methods are disclosed and described, it is to be understood that they are not limited to particular synthetic methods unless otherwise specified, nor to particular reagents unless otherwise specified, and therefore may, of course, vary. It is also understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, exemplary methods and materials are now described.

[0030] This disclosure describes the inventive concepts with reference to specific embodiments, but is intended to cover all modifications, equivalents, and alternatives of the inventive concepts consistent with this disclosure.

[0031] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0032] The phrase "consisting essentially of" limits the scope of a claim to those components recited with respect to the composition or steps recited with respect to the process, and to those that do not materially affect the basic and novel characteristic(s) of the claimed composition or claimed process. The phrase "consisting of" excludes any component, step, or element not recited in the claim. The phrase "comprising" is synonymous with "including," "containing," or "characterized by" and is inclusive or open-ended. "Comprising" does not exclude additional, unrecited components or steps.

[0033] As used herein, when referring to any numerical value, the term "about" means a value that falls within ±10% of the stated value.

[0034] Ranges may be expressed herein as from "about" one particular value and / or to "about" another particular value. When such a range is expressed, a further embodiment includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent "about," it will be understood that the particular value forms a further embodiment. It will further be understood that each of the endpoints of a range is significant both in relation to the other endpoint, and independently of the other endpoint. It is understood that several values are disclosed herein, and that each value is also disclosed herein as "about" that particular value in addition to the value itself. For example, if the value "10" is disclosed, then "about 10" is also disclosed. It is also understood that each unit between two particular units is disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

[0035] References herein and in the concluding claims to parts by weight of a particular element or component in a composition refer to the weight relationship of that element or component to any other element or component in the composition or item for which the part by weight is expressed. Thus, in a compound containing 2 parts by weight of component X and 5 parts by weight of component Y, X and Y are present in a weight ratio of 2:5, and are present in such ratio regardless of whether additional components are included in the compound.

[0036] As used herein, the terms "as needed" or "as needed" mean that the subsequently described event or circumstance may or may not occur, and that the description encompasses cases where the event or circumstance occurs and cases where the event or circumstance does not occur. In certain aspects, the disclosed methods can optionally include one or more additional steps, such as repeating or modifying the administering step.

[0037] As used herein, the term "subject" refers to the target of administration, e.g., a human. The term "subject" also encompasses domestic animals (e.g., cats, dogs, etc.), livestock (e.g., cows, horses, pigs, sheep, goats, etc.), and experimental animals (e.g., mice, rabbits, rats, guinea pigs, fruit flies, etc.). Thus, the subject of the methods disclosed herein may be a vertebrate, such as a mammal, fish, bird, reptile, or amphibian. Alternatively, the subject of the methods disclosed herein may be a human, non-human primate, horse, pig, rabbit, dog, sheep, goat, cow, cat, guinea pig, or rodent. The term does not denote a particular age or sex, and thus is intended to encompass adult and child subjects, as well as fetuses, regardless of gender. In some embodiments, the subject may be a human patient. In some embodiments, the subject may have cancer, be suspected of having cancer, or be at risk of developing cancer.

[0038] As used herein, the term "diagnosed" means having been subjected to examination by a person skilled in the art, e.g., a physician, and found to have a condition that can be diagnosed or treated by one or more of the disclosed antineoplastons, the disclosed pharmaceutical preparations, or any combination thereof, or by one or more of the disclosed methods. For example, "diagnosed to have a disease or disorder" means having been subjected to examination by a person skilled in the art, e.g., a physician, and found to have a condition (e.g., cancer) that can be treated by one or more of the disclosed antineoplastons, the disclosed pharmaceutical preparations, or any combination thereof, or by one or more of the disclosed methods. For example, "suspected of having a disease or disorder" can mean having been subjected to examination by a person skilled in the art, e.g., a physician, and found to have a condition (e.g., cancer) that is likely to be treatable by one or more of the disclosed antineoplastons, the disclosed pharmaceutical preparations, or any combination thereof, or by one or more of the disclosed methods. In some embodiments, the examination may be a physical examination and may involve various tests (e.g., blood tests, genotyping, biopsies, etc.), scans (e.g., CT scans, PET scans, etc.), and assays (e.g., enzyme assays), or combinations thereof.

[0039] "Patient" refers to a subject suffering from a disease or disorder (e.g., cancer, terminal cancer, metastatic cancer). In certain embodiments, a patient may refer to a subject diagnosed with or suspected of having a disease or disorder, such as cancer. In certain embodiments, a patient may refer to a subject diagnosed with or suspected of having a disease or disorder, and seeking or receiving treatment for a disease or disorder (e.g., cancer).

[0040] As used herein, phrases such as "identified as needing treatment for a disease or disorder" refer to the selection of a subject based on the need for treatment for a disease or disorder. For example, a subject can be identified as needing treatment for a disease or disorder (e.g., cancer) based on a previous diagnosis by a person skilled in the art, and can then be subjected to treatment for the cancer. In some embodiments, the identification can be performed by a person different from the person who makes the diagnosis. In some embodiments, the person who makes the diagnosis can also perform the administration.

[0041] As used herein, "inhibit," "inhibiting," and "inhibition" mean to attenuate or reduce an activity, level, response, condition, severity, disease, or other biological parameter. This can include, but is not limited to, the complete elimination of an activity, level, response, condition, severity, disease, or other biological parameter (e.g., one or more genomic aberrations, etc.). This can also include, for example, a 10% inhibition or reduction of an activity, level, response, condition, severity, disease, or other biological parameter (e.g., one or more genomic aberrations, etc.) compared to native or control levels (e.g., subjects not receiving a disclosed antineoplaston, a disclosed pharmaceutical formulation, or any combination thereof). Thus, in certain embodiments, inhibition or reduction can be a 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, or any amount therebetween reduction compared to native or control levels. In some embodiments, inhibition or reduction can be 10-20%, 20-30%, 30-40%, 40-50%, 50-60%, 60-70%, 70-80%, 80-90%, or 90-100% compared to native or control levels (e.g., subjects not receiving a disclosed antineoplaston, a disclosed pharmaceutical formulation, or any combination thereof). In some embodiments, inhibition or reduction can be 0-25%, 25-50%, 50-75%, or 75-100% compared to native or control levels. In some embodiments, native or control levels can be pre-disease or pre-disorder levels (e.g., pre-cancerous conditions).

[0042] The words "treat" or "treating" or "treatment" include palliative treatment, i.e., treatment designed to relieve symptoms rather than cure the disease, pathological condition, or disorder; preventative treatment, i.e., treatment directed to minimizing or partially or completely preventing the occurrence of the associated disease, pathological condition, or disorder; and supportive treatment, i.e., treatment used to supplement another specific therapy directed to ameliorating the associated disease, pathological condition, or disorder. In certain embodiments, these terms encompass any treatment of a subject, including a mammal (e.g., a human), and include (i) preventing an undesirable physiological change, disease, pathological condition, or disorder from occurring in a subject who may be predisposed to the disease but has not yet been diagnosed as having it, (ii) inhibiting a physiological change, disease, pathological condition, or disorder, i.e., halting its occurrence, or (iii) relieving a physiological change, disease, pathological condition, or disorder, i.e., causing regression of the disease. For example, in certain embodiments, treating a disease or disorder may reduce the severity of an established disease or disorder in a subject by 1% to 100% compared to a control (e.g., an individual without cancer). In certain embodiments, treating may refer to a 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% reduction in the severity of a disease or disorder (e.g., cancer). For example, treating a disease or disorder may reduce one or more symptoms of the disease or disorder in a subject by 1% to 100% compared to a control (e.g., an individual without cancer). In certain embodiments, treating can refer to a 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100% reduction in one or more symptoms of an established disease or disorder. It is understood that treating does not necessarily refer to a cure or complete removal or eradication of a disease or disorder. However, in certain embodiments, treating can refer to a cure or complete removal or eradication of a disease or disorder (e.g., cancer).

[0043] As used herein, the term "prevent" or "preventing" or "prevention" refers to preventing, avoiding, removing, forestalling, stopping, or impeding something from happening, especially by prior action. When reduce, inhibit, or prevent are used herein, it is understood that the use of the other two words is also expressly disclosed unless otherwise indicated. In certain embodiments, it is intended to prevent a disease or disorder associated with chromatin deregulation and / or chromatin dysregulation. The words "prevent," "preventing," and "prevention" also refer to prophylactic or preventative measures to protect a subject (e.g., an individual) from having a given disease or disorder (e.g., cancer) or related complications or to prevent the progression of those complications. In certain embodiments, it is intended to prevent metastasis.

[0044] As used herein, the terms "administering" and "administration" refer to any method of providing one or more of the disclosed antineoplastons, the disclosed pharmaceutical formulations, or any combination thereof to a subject. Such methods are well known to those skilled in the art and include, but are not limited to, oral administration, transdermal administration, administration by inhalation, nasal administration, topical administration, intrauterine administration, intratumoral administration, intrahepatic administration, intravaginal administration, ocular administration, intraauricular administration, otic administration, intracerebral administration, rectal administration, sublingual administration, buccal administration, and parenteral administration, including injections such as intravenous administration, intraCSF administration, intraarterial administration, intramuscular administration, and subcutaneous administration. Administration can also include administration into the hepatic artery or through the hepatic portal vein (HPV). Administration of a disclosed composition, a disclosed pharmaceutical composition, a disclosed therapeutic agent, a disclosed immunomodulator, a disclosed proteasome inhibitor, a disclosed small molecule, a disclosed endonuclease, a disclosed oligonucleotide, a disclosed RNA therapeutic, or any combination thereof can include direct administration into the CNS or PNS. Administration can be continuous or intermittent. Administration can include a combination of one or more routes. In certain embodiments, administering can include titrating a disclosed composition, a disclosed pharmaceutical composition, a disclosed therapeutic agent, a disclosed immunomodulator, a disclosed proteasome inhibitor, a disclosed small molecule, a disclosed endonuclease, a disclosed oligonucleotide, a disclosed RNA therapeutic, or any combination thereof to identify an effective dose and / or to identify an effective dose that induces only mild adverse and / or side effects.

[0045] As is known in the art, the disclosed small molecules can include any organic or inorganic material that is not a polymer. As is known in the art, the disclosed small molecules include large macromolecules, such as large proteins (e.g., proteins with a molecular weight greater than 2,000, greater than 3,000, greater than 4,000, greater than 5,000, greater than 6,000, greater than 7,000, greater than 8,000, greater than 9,000, or greater than 10,000), large nucleic acids (e.g., proteins with a molecular weight greater than 2,000, greater than 3,000, greater than 4 ... The term "small molecule" may exclude nucleic acids (e.g., nucleic acids having a molecular weight of more than 0, 5,000, 6,000, 7,000, 8,000, 9,000, or 10,000), or large polysaccharides (e.g., polysaccharides having a molecular weight of more than 2,000, 3,000, 4,000, 5,000, 6,000, 7,000, 8,000, 9,000, or 10,000). In certain embodiments, a "small molecule" may be, for example, a drug that can easily enter cells due to its low molecular weight. In certain embodiments, small molecules can be used in conjunction with the disclosed compositions or disclosed formulations in the disclosed methods.

[0046] In certain aspects, one of skill in the art can determine an effective dose, an effective schedule, and an effective route of administration of the disclosed antineoplastons, the disclosed pharmaceutical formulations, or any combination thereof, to treat or prevent a disease or disorder (e.g., cancer). In certain aspects, one of skill in the art can also change, vary, or modify aspects of the administering step to improve the effectiveness of the disclosed antineoplastons, the disclosed pharmaceutical formulations, or any combination thereof.

[0047] "Determining the amount" refers to both the absolute quantification of a particular analyte (e.g., a cancer biomarker) or the determination of the relative abundance of a particular analyte (e.g., a cancer biomarker). The phrase encompasses either direct or indirect measurement of abundance, or both.

[0048] As used herein, "modifying a method" can include altering or changing one or more features or aspects of one or more steps of the disclosed methods of treating and / or preventing cancer. In certain embodiments, the method can be altered by changing the amount of a disclosed precision cancer treatment, a disclosed antineoplaston, a disclosed pharmaceutical formulation, a disclosed anti-chemokine, a disclosed anti-cancer agent, a disclosed chemotherapeutic agent, or a combination thereof administered to a subject, by changing the frequency of administration of a disclosed precision cancer treatment, a disclosed antineoplaston, a disclosed pharmaceutical formulation, a disclosed anti-chemokine, a disclosed anti-cancer agent, a disclosed chemotherapeutic agent, or a combination thereof to a subject, by changing the duration over which a disclosed precision cancer treatment, a disclosed antineoplaston, a disclosed pharmaceutical formulation, a disclosed anti-chemokine, a disclosed anti-cancer agent, a disclosed chemotherapeutic agent, or a combination thereof is administered to a subject, or by substituting similar or equivalent components and / or reagents for one or more of the disclosed components and / or reagents. The same applies to all disclosed precision cancer treatments, disclosed antineoplastons, disclosed pharmaceutical formulations, disclosed anti-chemokines, disclosed anti-cancer agents, disclosed chemotherapeutic agents, or combinations thereof.

[0049] As used herein, the term "pharmaceutically acceptable carrier" refers to sterile aqueous or non-aqueous solutions, dispersions, suspensions, or emulsions, as well as sterile powders for reconstitution into sterile injectable solutions or dispersions immediately prior to use. Examples of suitable aqueous and non-aqueous carriers, diluents, solvents, or vehicles include water, ethanol, polyols (e.g., glycerol, propylene glycol, polyethylene glycol, etc.), carboxymethylcellulose and suitable mixtures thereof, vegetable oils (e.g., olive oil), and injectable organic esters such as ethyl oleate. In some embodiments, the pharmaceutical carrier used can be solid, liquid, or gaseous. In some embodiments, examples of solid carriers include lactose, terra alba, sucrose, talc, gelatin, agar, pectin, gum arabic, magnesium stearate, and stearic acid. In some embodiments, examples of liquid carriers include sugar syrup, peanut oil, olive oil, and water. In some embodiments, examples of gaseous carriers include carbon dioxide and nitrogen. Any convenient pharmaceutical medium can be used in preparing the disclosed compositions for oral dosage forms. For example, water, glycols, oils, alcohols, flavoring agents, preservatives, coloring agents, and the like can be used to form oral liquid preparations such as suspensions, elixirs, and solutions, while carriers such as starch, sugars, microcrystalline cellulose, diluents, granulating agents, lubricants, binders, disintegrants, and the like can be used to form oral solid preparations such as powders, capsules, and tablets. Tablets and capsules are the preferred oral dosage units for ease of administration, where solid pharmaceutical carriers are used. If necessary, tablets can be coated by standard aqueous or nonaqueous techniques. Proper fluidity can be maintained, for example, by using coating materials such as lecithin, by maintaining the required particle size in the case of dispersions, and by using surfactants. These compositions may also contain adjuvants such as preservatives, wetting agents, emulsifying agents, and dispersing agents. Prevention of the action of microorganisms can be ensured by including various antibacterial and antifungal agents, such as parabens, chlorobutanol, phenol, sorbic acid, and the like.It may also be desirable to include isotonic agents, such as sugars or sodium chloride. Prolonged absorption of injectable pharmaceutical forms can be achieved by including agents that delay absorption, such as aluminum monostearate and gelatin. Injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers such as polylactide-polyglycolide, poly(orthoesters), and poly(anhydrides). The rate of drug release can be controlled depending on the drug-to-polymer ratio and the nature of the particular polymer used. Depot injectable formulations are also prepared by entrapping the drug in liposomes or microemulsions that are compatible with body tissue. Injectable formulations can be sterilized, for example, by filtration through a bacteria-retaining filter, or by incorporating a sterilizing agent in the form of a sterile solid composition that can be dissolved or dispersed in sterile water or other sterile injectable medium immediately prior to use. Suitable inert carriers include sugars, such as lactose. It is desirable that at least 95% by weight of the particles of the active ingredient have an effective particle size in the range of 0.01 to 10 micrometers.

[0050] As used herein, the term "excipient" refers to an inert substance commonly used as a diluent, vehicle, preservative, binder, or stabilizer, including, but not limited to, proteins (e.g., serum albumin, etc.), amino acids (e.g., aspartic acid, glutamic acid, lysine, arginine, glycine, histidine, etc.), fatty acids and phospholipids (e.g., alkylsulfonates, caprylates, etc.), surfactants (e.g., SDS, polysorbates, nonionic surfactants, etc.), sugars (e.g., sucrose, maltose, trehalose, etc.), and polyols (e.g., mannitol, sorbitol, etc.). For reference, see also Remington's Pharmaceutical Sciences, (1990) Mack Publishing Co., Easton, Pa., the entire contents of which are incorporated herein by reference.In certain embodiments, acceptable carriers, additives, or stabilizers are nontoxic to recipients at the dosages and concentrations used herein and include, but are not limited to, buffers such as, but not limited to, phosphate, citric acid, and other organic acids; antioxidants, including ascorbic acid and methionine; preservatives (e.g., octadecyldimethylbenzylammonium chloride; hexamethonium chloride; benzalkonium chloride, benzethonium chloride; phenol, butyl, or benzyl alcohol; alkyl parabens such as methylparaben or propylparaben; catechol; resorcinol; cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; These may include proteins such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates, including glucose, mannose, or dextran; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose, or sorbitol; salt-forming counterions such as sodium; metal complexes (e.g., Zn-protein complexes); and / or non-ionic surfactants such as Tween®, Pluronic®, or polyethylene glycol (PEG).

[0051] As used herein, "concurrently" means (1) simultaneously in time or (2) at different times during the course of a common treatment schedule.

[0052] The term "contacting," as used herein, refers to bringing one or more of the disclosed precision cancer treatments, disclosed antineoplastons, disclosed pharmaceutical formulations, disclosed anti-chemokines, disclosed anti-cancer agents, disclosed chemotherapeutics, or combinations thereof, into contact with a target area or intended target area in a manner that allows the disclosed precision cancer treatments, disclosed antineoplastons, disclosed pharmaceutical formulations, disclosed anti-chemokines, disclosed anti-cancer agents, disclosed chemotherapeutics, or combinations thereof to directly or indirectly exert an effect on the intended target or targeted area. The target area or intended target area may be one or more of the subject's organs (e.g., lung, heart, liver, kidney, brain, etc.) that host cancerous cells. In certain embodiments, the target area or intended target area may be any cell or any organ affected by a disease or disorder (e.g., cancer). In certain embodiments, the target area or intended target area may be any organ, tissue, or cell affected by a disease or disorder (e.g., cancer).

[0053] As used herein, " determining " can refer to measuring or confirming the existence and severity of disease or disorder, such as cancer.The methods and techniques used to determine the existence and / or severity of disease or disorder are generally known in the medical field.For example, the method of identifying and / or diagnosing the existence, severity, or both of disease or disorder (such as cancer) is well known in the art.

[0054] As used herein, "effective amount" and "amount effective" may refer to an amount sufficient to achieve a desired result, such as, for example, treatment and / or prevention of a disease or disorder (e.g., cancer) or suspected disease or disorder. As used herein, the terms "effective amount" and "effective amount" may refer to an amount sufficient to achieve a desired effect on an undesired condition (e.g., cancer). For example, a "therapeutically effective amount" refers to an amount sufficient to achieve a desired therapeutic result or to have an effect on an undesired symptom, but generally insufficient to cause adverse side effects. In certain aspects, a "therapeutically effective amount" refers to the amount of a disclosed precision cancer treatment, a disclosed antineoplaston, a disclosed pharmaceutical formulation, a disclosed anti-chemokine, a disclosed anti-cancer agent, a disclosed chemotherapeutic agent, or a combination thereof that (i) treats a particular disease, condition, or disorder (e.g., cancer), (ii) attenuates, ameliorate, or eliminates one or more symptoms of a particular disease, condition, or disorder (e.g., cancer), or (iii) delays the onset of one or more symptoms of a particular disease, condition, or disorder (e.g., cancer) described herein. The specific therapeutically effective dose level for any particular patient will depend upon a variety of factors, including the disorder being treated and the severity of the disorder; the disclosed precision cancer treatment, disclosed antineoplaston, disclosed pharmaceutical formulation, disclosed antichemokine, disclosed anti-cancer agent, disclosed chemotherapeutic agent, or combination thereof used; the disclosed method used; the patient's age, weight, general health, sex, and diet; the time of administration; the route of administration; the excretion rate of the disclosed precision cancer treatment, disclosed antineoplaston, disclosed pharmaceutical formulation, disclosed antichemokine, disclosed anti-cancer agent, disclosed chemotherapeutic agent, or combination thereof used; the duration of treatment; the drugs used in combination or simultaneously with the disclosed precision cancer treatment, disclosed antineoplaston, disclosed pharmaceutical formulation, disclosed antichemokine, disclosed anti-cancer agent, disclosed chemotherapeutic agent, or combination thereof used, as well as other factors similarly well known in the medical arts.For example, it is well within the skill of the art to initiate a dose of a disclosed precision cancer treatment, a disclosed antineoplaston, a disclosed pharmaceutical formulation, a disclosed antichemokine, a disclosed anticancer agent, a disclosed chemotherapeutic agent, or a combination thereof at a level below that required to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is reached. If desired, the effective daily dose can then be divided into multiple doses for administration. Consequently, a single dose of a disclosed precision cancer treatment, a disclosed antineoplaston, a disclosed pharmaceutical formulation, a disclosed antichemokine, a disclosed anticancer agent, a disclosed chemotherapeutic agent, or a combination thereof can contain an amount or submultiple thereof that constitutes a daily dose. In the event of any contraindications, the dosage can be adjusted by an individual physician. The dosage can be varied and administered in one or more daily doses over one or several days. Guidance regarding appropriate dosages for a given class of pharmaceutical products can be found in the literature. In further various embodiments, the preparations can be administered in a "prophylactically effective amount," i.e., an amount effective to prevent a disease or condition, e.g., a disease or disorder resulting from loss, deficiency, and / or mutation of a protein or enzyme.

[0055] As used herein, "monoclonal antibody" refers to a homogeneous antibody population that is involved in highly specific recognition and binding to a single antigenic determinant, or epitope. Monoclonal antibodies are in contrast to polyclonal antibodies, which generally contain different antibodies directed against different antigenic determinants. The term "monoclonal antibody" encompasses both intact, full-length monoclonal antibodies as well as antibody fragments (e.g., Fab, Fab', F(ab')2, Fv, etc.), single-chain (scFv) variants, fusion proteins containing an antibody portion, and any other modified immunoglobulin molecule containing an antigen recognition site. Furthermore, "monoclonal antibody" refers to antibodies produced in several ways, including, but not limited to, by hybridoma, phage selection, recombinant expression, and transgenic animals.

[0056] As used herein, the term "humanized antibody" refers to a form of a non-human (e.g., murine) antibody that is a specific immunoglobulin chain, chimeric immunoglobulin, or fragment thereof that contains minimal non-human sequence. Generally, a humanized antibody is a human immunoglobulin in which residues from the complementarity-determining regions (CDRs) are replaced by residues from the CDRs of a non-human species (e.g., mouse, rat, rabbit, hamster, etc.) having the desired specificity, affinity, and capacity. In some cases, Fv framework region (FR) residues of the human immunoglobulin are replaced by corresponding residues of an antibody from a non-human species having the desired specificity, affinity, and capacity. Humanized antibodies can be further modified by substituting additional residues either within the Fv framework regions and / or within the replaced non-human residues to improve and optimize the antibody's specificity, affinity, and / or capacity. Generally, a humanized antibody will comprise at least one, and typically two or three, variable domains containing all or substantially all of the CDR regions corresponding to a non-human immunoglobulin, while all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody may also comprise at least a portion of an immunoglobulin constant region or domain (Fc), typically that of a human immunoglobulin.

[0057] An antibody that "selectively binds" or "specifically binds" to an epitope or receptor refers to an antibody that reacts or associates with the epitope or receptor more frequently, more rapidly, with a longer duration, with higher affinity, or with some combination of the above, than with alternative substances, including unrelated proteins. "Selectively binds" or "specifically binds" means, for example, that the antibody binds to a protein with a KD of about 0.1 mM or less, more usually about 1 μM or less. "Selectively binds" or "specifically binds" sometimes means that the antibody binds to a protein with a KD of about 0.1 mM or less, sometimes about 1 μM or less, sometimes about 0.1 μM or less, sometimes about 0.01 μM or less, and sometimes about 1 nM or less. It is understood that in certain embodiments, an antibody or binding moiety that specifically binds to a first target may or may not specifically bind to a second target. Thus, "specific binding" does not necessarily require (but can include) exclusive binding, e.g., binding to a single target.

[0058] Polyclonal antibodies can be prepared by any known method. Polyclonal antibodies are produced by immunizing animals (e.g., rabbits, rats, mice, donkeys, goats, etc.) with relevant antigens (purified peptide fragments, full-length recombinant proteins, fusion proteins, etc.) conjugated as needed with keyhole limpet hemocyanin (KLH), serum albumin, etc., diluted in sterile saline, and combined with an adjuvant (e.g., complete Freund's adjuvant or incomplete Freund's adjuvant) to form a stable emulsion, via multiple subcutaneous or intraperitoneal injections. Polyclonal antibodies are then recovered from the blood, ascites, etc. of the immunized animals. The collected blood is allowed to clot, and the serum is decanted, clarified by centrifugation, and assayed for antibody titer. Polyclonal antibodies can be purified from the serum or ascites according to standard methods in the art, including affinity chromatography, ion exchange chromatography, gel electrophoresis, dialysis, etc.

[0059] As used herein, the terms "precision medicine" and "precision cancer treatment" can be used interchangeably and refer to a method of administering a cancer treatment (e.g., ANP treatment) to a subject after measuring the subject's molecular markers to assess the likelihood of response or lack of response to a particular cancer treatment. In some embodiments, for example, the precision cancer treatment can include ANP and one or more other therapeutic agents (which can be determined using the disclosed genomic analysis). With respect to cancer treatment, precision medicine means measuring the subject's molecular markers to select a treatment that is most likely to benefit the subject while sparing the subject from treatments that are unlikely to benefit. In some embodiments, the molecular markers disclosed herein can be used to identify one or more precision cancer treatments to be administered to the subject herein, and / or can be determined by assessing the gene expression of one or more cancer-related genes. In some embodiments, the molecular markers disclosed herein can be used to identify one or more precision cancer treatments to be administered to the subject herein, and may be increased expression of one or more cancer-related genes compared to healthy subjects who do not have or are not suspected of having cancer. In some embodiments, the molecular markers disclosed herein can be used to identify one or more high-precision cancer treatments to be administered to a subject herein, and may be a reduction in the expression of one or more cancer-associated genes compared to healthy subjects who do not have or are not suspected of having cancer. In some embodiments, the molecular markers disclosed herein can be used to identify one or more high-precision cancer treatments to be administered to a subject herein, and may be base mutations and / or variants in the sequence of one or more cancer-associated genes compared to healthy subjects who do not have or are not suspected of having cancer.

[0060] As used herein, the terms "cancer" and "cancerous" refer to or describe a physiological condition in mammals in which a population of cells is characterized by unregulated cell growth. Examples of cancer include, but are not limited to, carcinoma, lymphoma, blastoma, sarcoma, and leukemia. More specific examples of such cancer include squamous cell carcinoma, small cell lung cancer, non-small cell lung cancer, lung adenocarcinoma, squamous cell carcinoma of the lung, peritoneal cancer, hepatocellular carcinoma, gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, breast cancer, colon cancer, colorectal cancer, endometrial or uterine cancer, salivary gland cancer, kidney cancer, liver cancer, prostate cancer, vulvar cancer, thyroid cancer, liver cancer, various types of head and neck cancer, various types of brain tumors, or any combination thereof.

[0061] The terms "proliferative disorder" and "proliferative disease" refer to disorders associated with abnormal cell proliferation, such as cancer.

[0062] "Tumor" and "neoplasm," as used herein, refer to any mass of tissue resulting from excessive cell growth or proliferation, either benign (non-cancerous) or malignant (cancerous), including precancerous lesions. "Metastasis," as used herein, refers to the process by which cancer spreads or migrates from its site of origin to other areas of the body, developing similar cancerous lesions in the new location. "Metastatic" or "metastasizing" cells are cells that lose adhesive contacts with neighboring cells and migrate from the primary site of disease via the bloodstream or lymphatics to invade neighboring body structures.

[0063] The terms "cancer stem cells" or "tumor stem cells" or "solid tumor stem cells" are used interchangeably herein to refer to a population of cells derived from solid tumors that (1) have extensive proliferative potential, (2) are capable of asymmetric cell division to generate one or more types of differentiated progeny with reduced proliferation or developmental potential, and (3) are capable of symmetric cell division for self-renewal or self-sustainment. These properties of "cancer stem cells" or "tumor stem cells" or "solid tumor stem cells" confer upon them the ability to form palpable tumors when serially transplanted into immunocompromised mice, compared with the majority of tumor cells that are unable to form tumors. Cancer stem cells undergo self-renewal versus differentiation in a chaotic manner, forming tumors with abnormal cell types that can change over time as mutations arise.

[0064] The terms "cancer cells" or "tumor cells" and grammatical equivalents refer to the entire population of cells derived from a tumor, including both non-tumorigenic cells, which make up the majority of the tumor cell population, and tumorigenic stem cells (cancer stem cells).

[0065] As used herein, "tumorigenicity" refers to the functional characteristics of solid tumor stem cells, including their ability to self-renew (giving rise to additional tumorigenic cancer stem cells) and to proliferate to generate all other tumor cells (differentiating and thus giving rise to non-tumorigenic tumor cells), which allows them to form tumors.

[0066] As used herein, the "tumorigenicity" of a tumor refers to the ability of a random sample of cells from the tumor to form a palpable tumor upon serial transplantation into immunocompromised mice.

[0067] As used herein, "immune-modulating" refers to the ability of a disclosed isolated nucleic acid molecule, a disclosed precision cancer treatment, a disclosed pharmaceutical formulation, or a disclosed agent to alter (modulate) one or more aspects of the immune system. The immune system functions to protect organisms from infection and from foreign antigens through cellular and humoral mechanisms involving lymphocytes, macrophages, and other antigen-presenting cells, which regulate each other through multiple cell-to-cell interactions and by producing soluble factors, including lymphokines and antibodies, that have autocrine, paracrine, and endocrine effects on immune cells.

[0068] As used herein, "immunomodulator" refers to an agent capable of adjusting a given immune response to a desired level (e.g., immune enhancement, immune suppression, or induction of immune tolerance). Examples of immune modulators include, but are not limited to, aspirin, azathioprine, belimumab, betamethasone dipropionate, betamethasone valerate, bortezomib, bredinin, ciazathioprine, cyclophosphamide, cyclosporine, deoxyspergualin, didemnin B, fluocinolone acetonide, folinic acid, ibuprofen, IL6 inhibitors (e.g., sarilumab), indomethacin, inebilizumab, intravenous gamma globulin (IVIG), methotrexate, methylprednisolone, mycophenolate mofetil, naproxen, prednisolone, fluoxetine ... The disclosed immunomodulators may include nisolone, prednisone, prednisolone-indomethacin, rapamycin, rituximab, sirolimus, sulindac, synthetic vaccine particles containing rapamycin (SVP-rapamycin or ImmTOR), thalidomide, tocilizumab, tolmetin, triamcinolone acetonide, anti-CD3 antibody, anti-CD4 antibody, anti-CD19 antibody, anti-CD20 antibody, anti-CD22 antibody, anti-CD40 antibody, anti-FcRN antibody, anti-IL6 antibody, anti-IGF1R antibody, IL2 mutein, BTK inhibitor, or a combination thereof. In certain embodiments, the disclosed immunomodulators may include one or more Treg (regulatory T cell) infusions (e.g., antigen-specific Treg cells for AAV). In certain embodiments, the disclosed immunomodulators may be bortezomib or SVP-rapamycin. In certain embodiments, immune modulators can be administered by any suitable route of administration, including, but not limited to, intrauterine, intraCSF, intrathecal, intravenous, subcutaneous, transdermally, intradermal, intramuscular, oral, transcutaneously, intraperitoneally (IP), or intravaginally. In certain embodiments, the disclosed immune modulators can be administered using a combination of routes. Administration can also include administration into the hepatic artery or through the hepatic portal vein (HPV). Administration of the immune modulator can be continuous or intermittent, and administration can include a combination of one or more routes.

[0069] As used herein, the term "package insert" is used to refer to instructions customarily included in commercial packaging of a therapeutic product that contain information regarding the indications, use, dosage, administration, contraindications and / or warnings regarding the use of such therapeutic product.

[0070] As used herein, the term "in combination" in the context of the administration of other therapies (e.g., other agents) includes the use of more than one therapy (e.g., drug therapy). Administration "in combination with" one or more other therapeutic agents includes simultaneous (e.g., concurrent) and consecutive administration in any order. The use of the term "in combination" does not restrict the order in which therapies are administered to a subject. As a non-limiting example, a subject having or diagnosed with cancer may be administered a first treatment (e.g., a disclosed precision cancer treatment, a disclosed antineoplaston, a disclosed pharmaceutical formulation, a disclosed anti-chemokine, a disclosed anti-cancer agent, a disclosed chemotherapeutic agent, or a combination thereof) before (e.g., 1 minute, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 12 hours before) administering a second treatment (e.g., a disclosed precision cancer treatment, a disclosed antineoplaston, a disclosed pharmaceutical formulation, a disclosed anti-chemokine, a disclosed anti-cancer agent, a disclosed chemotherapeutic agent, or a combination thereof). The therapeutic agent can be administered before, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or 12 weeks prior to, concurrently with, or after (e.g., 1 minute, 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, or 12 weeks or more after) administration.

[0071] Disclosed herein are the disclosed isolated nucleic acid molecules, the disclosed precision cancer treatments, or the disclosed pharmaceutical preparations, as well as the disclosed isolated nucleic acid molecules used in the methods disclosed herein, the disclosed precision cancer treatments, or the disclosed pharmaceutical preparations. These and other materials are disclosed herein, and when combinations, subsets, interactions, groups, etc. of these materials are disclosed, it is understood that although specific reference to each of the various individual compounds and collective combinations and permutations of these compounds may not be explicitly disclosed, each is specifically contemplated and described herein. For example, when a particular compound is disclosed and discussed, and several modifications that can be made to several molecules containing that compound are discussed, unless otherwise specified, each and every combination and permutation of possible compounds and modifications is specifically contemplated. Thus, if classes of molecules A, B, and C and classes of molecules D, E, and F are disclosed, and an example of combination molecule A-D is disclosed, each is intended to mean the combination individually and collectively, even if not individually set forth, and A-E, A-F, B-D, B-E, B-F, C-D, C-E, and C-F are considered disclosed. Likewise, any subset or combination of these is also disclosed. Thus, for example, subgroups of A-E, B-F, and C-E are also considered disclosed. This concept applies to all aspects of the present application, including, but not limited to, steps in methods of making and using the compositions of the present invention. Thus, where there are various additional steps that can be performed, it is understood that each of these additional steps can be performed with any specifically disclosed method or disclosed embodiment or combination of disclosed methods or disclosed embodiments.

[0072] B. Compositions for Use in the Disclosed Methods 1. Antineoplastons Disclosed herein are compositions comprising one or more antineoplastons. Antineoplastons (ANPs) are peptides, amino acid derivatives, and carboxylic acids that were originally isolated from the blood and urine of healthy subjects.

[0073] Atengenal (A10) may contain synthetic phenylacetylglutaminate sodium (PG) and phenylacetylisoglutaminate sodium (iso-PG) in a 4:1 ratio. PG has a molecular weight of 286.26 and an empirical formula of C 13 H 15 N2NaO4. PG can be synthesized by the reaction of phenylacetyl chloride and L-glutamine in an aqueous solution containing sodium bicarbonate. PG is a hygroscopic white powder with a melting point of approximately 102°C and is highly soluble in water. The structural formula of PG is: [ka] is.

[0074] Iso-PG has a molecular weight of 286.26 and the empirical formula C 13 H 15 N2NaO4. Iso-PG can be synthesized by reacting phenylacetyl chloride with L-glutamine in an aqueous solution containing sodium bicarbonate to give PG, which can then be heated at 160°C under vacuum to give A10C (3-phenylacetylamino-2,6-piperidinedione). Treatment of A10C with sodium hydroxide can produce a 4:1 mixture of PG and iso-PG. Iso-PG is a white powder with a melting point of approximately 175-176°C and is soluble in water. The structural formula of iso-PG is: [ka] is.

[0075] Astugenal (AS2-1) may contain phenylacetate (PN) and PG in a 4:1 ratio. PN is characterized by a molecular weight of 158.63 and an empirical formula of C8H8NaO2. PN can be synthesized by refluxing benzyl cyanide with dilute sulfuric or hydrochloric acid. The melting point of PN in solid form is approximately 76.5°C. The structural formula of PN is: [ka] is.

[0076] As used herein, "antineoplaston (ANP) treatment" can refer to administering to a subject or patient an "ANP therapeutic composition" or a disclosed composition or a pharmaceutical formulation containing one or more antineoplastons (e.g., a therapeutically effective amount of attengenal (A10), astugenal (AS2-1), or any combination thereof) by any route of administration.

[0077] In some embodiments, the disclosed ANP treatments can be used as pan-tumor treatments.

[0078] 2. Formulation Disclosed herein are pharmaceutical formulations that include one or more antineoplastons and one or more pharmaceutically acceptable carriers.

[0079] In certain aspects of the disclosed pharmaceutical formulations, the disclosed antineoplastons can include phenylacetate, phenylacetylglutaminate, sodium phenylacetylglutamate, sodium phenylacetylisoglutamate, or any combination thereof.

[0080] In certain embodiments of the disclosed pharmaceutical formulations, the one or more disclosed antineoplastons can include sodium phenylacetylglutamate (PG) and sodium phenylacetylisoglutamate (iso-PG). In certain embodiments of the disclosed pharmaceutical formulations, the disclosed ratio of sodium phenylacetylglutamate (PG) to sodium phenylacetylisoglutamate (iso-PG) can be about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1, or about 1:1. In certain embodiments of the disclosed pharmaceutical formulations, the disclosed ratio of sodium phenylacetylglutamate (PG) to sodium phenylacetylisoglutamate (iso-PG) can range from about 10:1 to about 1:10. In certain embodiments of the disclosed pharmaceutical formulations, the disclosed ratio of sodium phenylacetylglutamate (PG) to sodium phenylacetylisoglutamate (iso-PG) can be about 4:1. In certain embodiments, a therapeutically effective amount of the disclosed pharmaceutical formulations can include from about 0.1 g / kg / day to about 20 g / kg / day.

[0081] In certain embodiments of the disclosed pharmaceutical formulations, the one or more disclosed antineoplastons can include phenylacetate (PN) and phenylacetylglutamate (PG). In certain embodiments of the disclosed pharmaceutical formulations, the disclosed ratio of phenylacetate (PN) to phenylacetylglutamate (PG) can be about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1, or about 1:1. In certain embodiments of the disclosed pharmaceutical formulations, the disclosed ratio of phenylacetate (PN) to phenylacetylglutamate (PG) can range from about 10:1 to about 1:10. In certain embodiments of the disclosed pharmaceutical formulations, the disclosed ratio of phenylacetate (PN) to phenylacetylglutamate (PG) can be about 4:1. In certain embodiments, a therapeutically effective amount of the disclosed pharmaceutical formulations can include from about 0.08 g / kg / day to about 0.6 g / kg / day.

[0082] For example, in some embodiments, pazopanib and / or sorafenib can be orally administered to a subject at a dose of about 1 mg / kg / day to about 12 mg / kg / day, or 2 mg / kg / day to about 6 mg / kg / day. In some embodiments, the disclosed optimal dose of pazopanib and / or sorafenib can be about 3 mg / kg / day. In some embodiments, dasatinib can be orally administered to a subject at a dose of about 0.3 mg / kg / day to about 2.0 mg / kg / day, or about 0.7 mg / kg / day to about 1.4 mg / kg / day. In some embodiments, the disclosed optimal dose of dasatinib can be about 0.7 mg / kg / day. In some embodiments, everolimus can be orally administered to a subject at a dose of about 0.03 mg / kg / day to about 0.15 mg / kg / day, or about 0.03 mg / kg / day to about 0.10 mg / kg / day. In some embodiments, the disclosed optimal dose of everolimus may be about 0.07 mg / kg / day.

[0083] In certain embodiments, the disclosed pharmaceutical formulations comprising one or more antineoplastons can reduce and / or eliminate the number and / or type of genomic abnormalities. For example, in certain embodiments, if a subject initially has X number of genomic abnormalities, after administration of a disclosed pharmaceutical formulation, the subject has some number of genomic abnormalities that is less than X. In certain embodiments, the disclosed pharmaceutical formulations comprising one or more antineoplastons can prevent and / or reduce metastasis. In certain embodiments, the disclosed pharmaceutical formulations comprising one or more antineoplastons can prolong the survival of a subject. In certain embodiments, the disclosed pharmaceutical formulations comprising one or more antineoplastons can improve the survival chances of a subject. In certain embodiments, the disclosed pharmaceutical formulations comprising one or more antineoplastons may increase the subject's chances of survival, extend the length of time before metastasis, reduce the likelihood of surgical intervention, reduce the need to administer one or more additional therapeutic agents or regimens, reduce the size of one or more tumors in a subject, eliminate one or more tumors in a subject, reduce the prevalence of and / or eliminate one or more genomic abnormalities, restore normal metabolism of one or more organ systems in a subject, restore one or more aspects of cellular homeostasis and / or cellular functionality, and / or metabolic dysregulation, or any combination thereof.

[0084] In certain embodiments, the disclosed pharmaceutical formulations comprising one or more antineoplastons can protect a subject from metastasis, hi certain embodiments, the disclosed pharmaceutical formulations comprising one or more antineoplastons can reduce the risk of developing metastasis.

[0085] In certain embodiments, restoring one or more aspects of cellular homeostasis and / or cellular functionality may include one or more of the following: (i) correcting cellular starvation in one or more cell types (e.g., hepatocytes and muscle cells, etc.); (ii) normalizing aspects of the autophagy pathway (e.g., correcting, preventing, reducing, and / or reversing autophagy, etc.); (iii) improving, enhancing, restoring, and / or preserving mitochondrial functionality and / or structural integrity; and (iv) organelle functionality and / or structure. (v) preventing, slowing, and / or eliminating hypoglycemia, ketosis, and / or other liver abnormalities, (vi) correcting liver enzyme dysregulation, (vii) reversing, inhibiting, preventing, stabilizing, and / or slowing tumor metastasis, (viii) reversing, inhibiting, preventing, stabilizing, and / or slowing tumor growth and / or cancer spread, or (ix) any combination thereof. In certain embodiments, restoring one or more aspects of cellular homeostasis can include, for example, improving, enhancing, restoring, and / or preserving one or more aspects of the structural and / or functional integrity of cells in an organ or system affected by cancer.

[0086] In certain embodiments, the disclosed pharmaceutical formulations comprising one or more antineoplastons can include one or more chemotherapeutic agents. In certain embodiments, the disclosed chemotherapeutic agents can include anthracyclines, vinca alkaloids, alkylating agents, immune cell antibodies, antimetabolites, TNFR glucocorticoid-inducible TNFR-related protein (GITR) agonists, proteasome inhibitors, immunomodulators, or any combination thereof. In certain embodiments, the disclosed chemotherapeutic agents include 5-fluorouracil (Adrucil, Efudex), 6-mercaptopurine (Purinethol), 6-thioguanine, aclarubicin or aclacinomycin A, alemtuzumab (Lemtrada), anastrozole (Arimidex), bicalutamide (Casodex), bleomycin sulfate (Blenoxane), bortezomib (Velcade), busulfan (Myxomycin), or cyclosporine (Cyclosporin). eran), injectable busulfan (Busulfex), capecitabine (Xeloda), carboplatin (Paraplatin), carmustine (BiCNU), chlorambucil (Leukeran), cisplatin (Platinol), cladribine (Leustatin), Cosmegan, cyclophosphamide (Cytoxan or Neosar), cyclophosphamide, cytarabine liposome injection (DepoCyt), Cytara daunorubicin, cytosine arabinoside (Cytosar-U), dacarbazine (DTIC-Dome), dactinomycin (Cosmegen), daunorubicin citrate liposomal injection (DaunoXome), daunorubicin hydrochloride (Cerubidine), dexamethasone, docetaxel (Taxotere), doxorubicin hydrochloride (Adriamycin, Rubex), etoposide (Vepesid), fludarabine phosphate (Fludara) ), flutamide (Eulexin), folate antagonists, gemcitabine (difluorodeoxycytidine), gemtuzumab, gliotoxin, hydroxyurea (Hydrea), idarubicin (Idamycin), ifosfamide (IFEX), ifosfamide, irinotecan (Camptosar), L-asparaginase (ELSPAR), lenalidomide), leucovorin calcium, melphalan (Alkeran), melphalan,Methotrexate (Folex), mitoxantrone (Novantrone), Mylotarg, N4-pentoxycarbonyl-5-deoxy-5-fluorocytidine, nab-paclitaxel (Abraxane), paclitaxel (Taxol), pentostatin, phoenix (yttrium-90 / MX-DTPA), carmustine-containing polipheprosan 20 implant (Gliadel), purine analogs and adenosine deaminase inhibitors (fludarabine), pi The therapeutic agent may include a rimidine analog, rituximab, tamoxifen citrate (Nolvadex), temozolomide, teniposide (Vumon), tezacitibine, thalidomide or a thalidomide derivative, thiotepa, tirapazamine (Tirazone), injectable topotecan hydrochloride (Hycamptin), tositumomab, vinblastine (Velban), vinblastine, vincristine (Oncovin), vindesine, vinorelbine (Navelbine), or any combination thereof.

[0087] In certain embodiments, the disclosed pharmaceutical formulations comprising one or more antineoplastons can include anti-chemokine therapies that enhance resident memory T cell formation in tumor-free tissue. In certain embodiments, the disclosed anti-chemokine therapies can include one or more antibodies to CCL1, CCL2, CCL4, CCL17, CCL19, CCL21, CCL22, CCL25, CXCL9, CXCL10, CXCL11, CXCL12, CXCL13, CCR2, CCR5, CCR7, CCR8, CCR9, CXCR3, CXCR4, CXCR5, CX3CL1, CX3CR1, or any combination thereof.

[0088] In certain embodiments, the disclosed pharmaceutical formulations comprising one or more antineoplastons can be prepared for systemic or direct administration. In certain embodiments, the disclosed pharmaceutical formulations can be prepared for oral administration, intravenous administration, intratumoral administration, intraperitoneal administration, or any combination thereof. In certain embodiments, the disclosed pharmaceutical formulations can be prepared for any administration method disclosed herein. In certain embodiments, the disclosed pharmaceutical formulations can be prepared for administration by multiple routes, either in parallel or sequentially. For example, in certain embodiments, the disclosed pharmaceutical formulations can be administered intratumorally first, then intravenously. In certain embodiments, the disclosed pharmaceutical formulations can be administered intratumorally first, then orally. A skilled clinical practitioner can determine the best route of administration for a subject at a given time.

[0089] In certain embodiments, the disclosed pharmaceutical formulations comprising one or more disclosed antineoplastons may comprise (i) one or more active agents, (ii) biologically active agents, (iii) one or more pharmaceutically active agents, (iv) one or more immune-based therapeutic agents, (v) one or more clinically approved agents, or (vi) a combination thereof. In certain embodiments, the disclosed pharmaceutical formulations may comprise one or more immune modulators. In certain embodiments, the disclosed pharmaceutical formulations may comprise one or more proteasome inhibitors. In certain embodiments, the disclosed pharmaceutical formulations may comprise one or more immunosuppressants or immunosuppressants. In certain embodiments, the immunosuppressant may be antithymocyte globulin (ATG), cyclosporine (CSP), mycophenolate mofetil (MMF), or a combination thereof. In certain embodiments, the disclosed pharmaceutical formulations can include an anaplerotic agent (e.g., a C7 compound such as triheptanoin or MCT).

[0090] In some embodiments, the disclosed pharmaceutically acceptable carriers can include any of the disclosed carriers. In some embodiments, the disclosed pharmaceutically acceptable carriers can include any of the disclosed additives.

[0091] In certain embodiments, the disclosed pharmaceutical formulations can be packaged in unit dosage forms such as tablets, pills, capsules, powders, granules, solutions or suspensions, or suppositories for oral, parenteral, or rectal administration, or for administration by inhalation or insufflation.

[0092] In some embodiments, the disclosed pharmaceutical formulations can be used as pan-tumor treatments.

[0093] C. Methods of Treating and / or Preventing Cancer Disclosed herein are methods of treating and / or preventing cancer, the methods comprising administering a precision cancer treatment to a subject in need thereof, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment.

[0094] Disclosed herein are methods of treating cancer, the method comprising obtaining a biological sample from a subject in need thereof; subjecting the biological sample to cell-free DNA (cfDNA) analysis; diagnosing the subject as in need of a precision cancer treatment if the expression and / or amount of one or more genomic aberrations in the biological sample is greater than the expression and / or amount of the same one or more genomic aberrations in a control sample; administering the precision cancer treatment to the subject; and measuring the subject's tumor response and / or the subject's molecular response.

[0095] Disclosed herein is a method of treating cancer, comprising obtaining a biological sample from a subject in need thereof; subjecting the biological sample to cell-free DNA (cfDNA) analysis; diagnosing the subject as in need of a precision cancer treatment if the expression and / or amount of one or more genomic aberrations in the biological sample is greater than the expression and / or amount of the same one or more genomic aberrations in a control sample; and administering the precision cancer treatment to the subject, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment and wherein the subject's life expectancy is extended.

[0096] Disclosed herein is a method of treating cancer, comprising obtaining a biological sample from a subject in need thereof; subjecting the biological sample to cell-free DNA (cfDNA) analysis, wherein the expression and / or amount of one or more genomic aberrations in the biological sample is greater than the expression and / or amount of the same one or more genomic aberrations in a control sample, diagnosing the subject as being in need of a precision cancer treatment; and administering the precision cancer treatment to the subject, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment.

[0097] In some embodiments, the disclosed high-precision cancer treatments may include one or more antineoplastons or may include compositions comprising one or more antineoplastons. In some embodiments, the disclosed antineoplastons may include phenylacetate, phenylacetylglutamate, sodium phenylacetylglutamate, sodium phenylacetylisoglutamate, or any combination thereof. In some embodiments, the disclosed compositions comprising one or more antineoplastons may include phenylacetate, phenylacetylglutamate, sodium phenylacetylglutamate, sodium phenylacetylisoglutamate, or any combination thereof.

[0098] In some embodiments, compositions comprising one or more disclosed antineoplastons can include a pharmaceutically acceptable carrier. In some embodiments, the one or more disclosed antineoplastons can include sodium phenylacetylglutamate (PG) and sodium phenylacetylisoglutamate (iso-PG). In some embodiments, the disclosed ratio of sodium phenylacetylglutamate (PG) to sodium phenylacetylisoglutamate (iso-PG) can be about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1, or about 1:1. In some embodiments, the disclosed ratio of sodium phenylacetylglutamate (PG) to sodium phenylacetylisoglutamate (iso-PG) can range from about 10:1 to about 1:10. In some embodiments, the disclosed ratio of sodium phenylacetylglutamate (PG) to sodium phenylacetylisoglutamate (iso-PG) can be about 4:1. In some embodiments, the disclosed dose of one or more antineoplastons can include from about 0.1 g / kg / day to about 20 g / kg / day. In some embodiments, the disclosed therapeutically effective dose of one or more antineoplastons can include from about 0.1 g / kg / day to about 20 g / kg / day. In some embodiments, the disclosed dose of sodium phenylacetylglutamate (PG) can include from about 0.4 g / kg / day to about 16 g / kg / day, and the disclosed dose of sodium phenylacetylisoglutamate (iso-PG) can include from about 0.1 g / kg / day to about 4 g / kg / day. In some embodiments, the disclosed therapeutically effective amount of sodium phenylacetylglutamate (PG) can include from about 0.4 g / kg / day to about 16 g / kg / day. In some embodiments, the disclosed therapeutically effective amount of sodium phenylacetylisoglutamate (iso-PG) can include from about 0.1 g / kg / day to about 4 g / kg / day.

[0099] In some embodiments, the disclosed one or more antineoplastons can include phenylacetate (PN) and phenylacetylglutamate (PG). In some embodiments, the disclosed ratio of phenylacetate (PN) to phenylacetylglutamate (PG) can be about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1, or about 1:1. In some embodiments, the disclosed ratio of phenylacetate (PN) to phenylacetylglutamate (PG) can range from about 10:1 to about 1:10. In some embodiments, the disclosed ratio of phenylacetate (PN) to phenylacetylglutamate (PG) can be about 4:1. In some embodiments, the dose of the disclosed one or more antineoplastons can include about 0.08 g / kg / day to about 0.6 g / kg / day. In certain embodiments, a therapeutically effective dose of one or more disclosed antineoplastons can include from about 0.08 g / kg / day to about 0.6 g / kg / day. In certain embodiments, a disclosed dose of phenylacetate (PN) can include from about 0.064 g / kg / day to about 0.48 g / kg / day, and a disclosed dose of phenylacetylglutamate (PG) can include from about 0.016 g / kg / day to about 0.12 g / kg / day. In certain embodiments, a therapeutically effective dose of phenylacetate (PN) can include from about 0.064 g / kg / day to about 0.48 g / kg / day, and a therapeutically effective dose of phenylacetylglutamate (PG) can include from about 0.016 g / kg / day to about 0.12 g / kg / day.

[0100] In some embodiments of the disclosed methods for treating and / or preventing cancer, the step of administering the disclosed high-precision cancer treatment can include intravenous administration. In some embodiments, the disclosed high-precision cancer treatment can be administered intravenously to a subject using, for example, a dual-channel infusion pump or two single-channel pumps and a central venous catheter. In some embodiments, the disclosed IV administration of the disclosed high-precision cancer treatment can be performed once every four hours at an infusion rate of about 50 mL per hour to about 250 mL per hour (e.g., about 50 mL per hour, about 75 mL per hour, about 100 mL per hour, about 125 mL per hour, about 150 mL per hour, about 175 mL per hour, about 200 mL per hour, about 225 mL per hour, about 250 mL per hour), depending on the subject's age and condition / tolerance.

[0101] In certain embodiments, the disclosed methods of treating and / or preventing cancer can include titrating a dose of a disclosed high-precision cancer treatment. In certain embodiments, the disclosed methods of treating and / or preventing cancer can include titrating a dose of A10, AS2-1, or a combination thereof. In certain embodiments, the disclosed methods of treating and / or preventing cancer can include titrating a dose of a disclosed composition, a disclosed pharmaceutical composition, a disclosed therapeutic agent, a disclosed immunomodulator, a disclosed proteasome inhibitor, a disclosed small molecule, a disclosed endonuclease, a disclosed oligonucleotide, a disclosed RNA therapeutic, or any combination thereof to identify an effective dose and / or to identify an effective dose that induces only mild adverse and / or side effects.

[0102] In certain embodiments, the disclosed methods of treating and / or preventing cancer can include titrating a dose of a disclosed high-precision cancer treatment for a particular or disclosed subject. In certain embodiments, the disclosed methods of treating and / or preventing cancer can include titrating a dose of A10, AS2-1, or a combination thereof for a particular or disclosed subject. In certain embodiments, the disclosed methods of treating and / or preventing cancer can include titrating a dose of a disclosed composition, a disclosed pharmaceutical composition, a disclosed therapeutic agent, a disclosed immunomodulator, a disclosed proteasome inhibitor, a disclosed small molecule, a disclosed endonuclease, a disclosed oligonucleotide, a disclosed RNA therapeutic, or any combination thereof to identify an effective dose for a particular or disclosed subject and / or to identify an effective dose that induces only mild adverse and / or side effects.

[0103] In some embodiments, the administering step comprises administering to the subject a maximum tolerated dose of A10, AS2-1, or both. In some embodiments, the administering step comprises administering to the subject a less than maximum tolerated dose of A10, AS2-1, or both.

[0104] In some embodiments, IV administration of the disclosed high-precision cancer treatments can include outpatient settings. In some embodiments, A10 can be administered before, concurrently with, or after AS2-1 administration. In some embodiments, AS2-1 can be administered before, concurrently with, or after A10 administration. In some embodiments, the order in which one or more antineoplastons are administered can be changed during the treatment regimen.

[0105] In some embodiments, the disclosed methods for treating and / or preventing cancer may further include obtaining a biological sample from a subject before administering a disclosed high-precision cancer treatment. In some embodiments, the disclosed methods for treating and / or preventing cancer may further include obtaining a biological sample from a subject after administering a disclosed high-precision cancer treatment. In some embodiments, the disclosed methods for treating and / or preventing cancer may further include subjecting the biological sample to cell-free DNA (cfDNA) analysis. cfDNA analysis is known to those skilled in the art. In some embodiments, the disclosed cfDNA analysis can be repeated one or more times. In some embodiments, the disclosed obtaining step can be repeated one or more times.

[0106] In some embodiments of the disclosed methods for treating and / or preventing cancer, the disclosed cfDNA analysis can comprise next-generation sequencing.In some embodiments, next-generation sequencing (NGS) can comprise the use of one or more commercially available platforms.Commercially available NGS sequencing platforms can include, for example, Guardant360 CDx (Guardant Health, Inc.), FoundationOne CDx (F1CDx) (Foundation Medicine, Inc.) or Tempus xT (Tempus).

[0107] In certain embodiments of the disclosed methods of treating and / or preventing cancer, the disclosed cancer-associated gene is selected from the group consisting of ABL1, ABL2, ACO2, ACTB, ACVR1B, AKT, AKT1, AKT2, AKT3, ALK, AMER11, APC, AR, ARAF, ARFRP1, ARID1A, ARID1B, ARID2, ASK, ASPM, ASXL1, ATF1, ATF3, ATM, ATR, ATRX, AURKA, AURKB, AXIN1, AXL, BAD, BAGE, BAGE2, BAP1, BARD1, BAX, BCL2, BCL2L1, BCL2L2, BCL6 , BCMA, BCOR, BCORL1, BDNF, BLM, BMPR1A, BRAF, BRCA1, BRCA2, BRD4, BRIP1, BTG1, BTK, BUB1, C10ORF54, CAGE1, CARD11, CASP5, CBFB, CBL, CCL1, CCL11, CCL 13, CCL14, CCL15, CCL16, CCL17, CCL18, CCL19, CCL2, CCL20, CCL21, CCL22, CCL23, CCL24, CCL25, CCL26, CCL27, CCL28, CCL3, CCL4, CCL5, CCL7, CCL8, CCNA 2, CCNB 1, CCNB 2, CCND, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCR1, CCR10, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CD123, CD19, CD20, CD25, CD274, CD2 76, CD30, CD33, CD4, CD79A, CD79B, CD8, CD80, CD86, CDC, CDC2, CDC20, CDC25A, CDC25B, CDC25C, CDC42, CDC6, CDC6; CDC7, CDC73, CDCA8, CDH1, C DK12, CDK2, CDK3, CDK4, CDK6, CDK8, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, CEA, CEBPA, CFS1, CHD2, CHD4, CHEK1, CHEK2, CHK-1, CIC, CLDND1 , CNE2, CREBBP, CRKL, CRLF2, CSF1, CSF1R, CSF3, CTAG1, CTAG1B, CTAG2, CTAG4, CTAG5, CTAG6, CTAG9, CTCF, CTLA4, CTNNA1, CTNNB1, CUL3, CXCL1,<h2 style=";text-align:left;direction:ltr">CXCL10、CXCL11、CXCL12、CXCL13、CXCL14、CXCL16、CXCL17、CXCL2、CXCL3、C XCL5, CXCL6, CXCL9, CXCR1, CXCR2, CXCR3, CXCR5, CXCR6, CYLD, DAXX, DCC, D DR2、DEPTOR、DICER1、DLD、DLST、DNMT3A、DOT1L、DUSP1、DUSP6、E2F1、EBNA1 、EBNA2、EGFR、EMSY、ENOX2、EP300、EPCAM、EPHA3、EPHA5、EPHA7、EPHB1、ERBB 2、ERBB3、ERBB4、ERCC1、EREG、ERG、ERK、ERRFI1、ESR1、EWSR1、EZH2、FAM46C 、FANCA、FANCC、FANCD2、FANCE、FANCF、FANCG、FANCL、FAS、FAT1、FBXW7、FGF 10、FGF14、FGF19、FGF23、FGF3、FGF4、FGF6、FGFR、FGFR1、FGFR2、FGFR3、FGF R4、FH、FLCN、FLI1、FLT1、FLT3、FLT4、FOLH1、FOLR1、FOXL2、FOXP1、FRS2、FUB P1、GABRA6、GADD45A、GAGE1、GAGE10、GAGE12D、GAGE12F、GAGE12J、GAGE13、 GAGE2A、GAGE2B、GAGE2C、GAGE2D、GAGE2E、GAGE4、GART、GATA1、GATA2、GATA 3、GATA4、GATA6、GID4、GLI1、GNA、GNA11、GNA13、GNAQ、GNAS、GPNMB、GPR124 、GRIN2A、GRM3、GSK3B、H3F3A、HAVCR2、HDAC、HDAC1、HDAC5、HGF、HHLA2、HIF1 HIF1A, HIST1H1D, HNF1A, HRAS, HSD3B1, HSP90AA1, ICOSLG, IDH1, IDH2, IDH3A, IDH3B, IDO, IGF1R, IGF2, IKBKE, IKZF1, IL1, IL15, IL1A, IL1B, IL6, IL 7R、IL8、INHBA、INPP4B、IRF2、IRF4、IRS2、JAK1、JAK2、JAK3、JUN、KDM5A、KD M5C、KDM6A、KDR、KEAP、KEL、KIT、KLHL6、KLK3、KRAS、LAG1、LAG3、LMO1、LMP1、LRP1B、LYN、LZTR1、MAD2L1、MAGEA1、MAGEA10、MAGEA12、MAGEA2、MAGEA3、MAGEA4、MAGEA5、MAGEA6、MAGEA7、MAGEA8、MAGEA9、MAGEB1、MAGEB10、MAGEB16、MAGEB18、MAGEB2、MAGEB3、MAGEB4、MAGEB6、MAGEC1、MAGEC2、MAGEC3、MAGED1、MAGED2、MAGED4、MAGED4B、MAGEE1、MAGEE2、MAGEF1、MAGEH1、MAGEL2、MAGI2、MAP2K1、MAP2K2、MAP2K4、MAP3K1、MAP3K6、MAPK、MCL1、MCM、MCM2、MCM3、MCM4、MCM5、MCM6、MCM7、MDH1、MDM2、MDM4、MED12、MEF26、MEF2B、MEN1、MET、MITF、MLH1、MLL、MLL2、MLL3、MPL、MRE11A、MSH2、MSH6、MTOR、MUC1、MUTYH、MYC、MYCL、MYCN、MYD88、MYH、MYST3、NCR3LG1、Netrin、NF1、NF2、NFE2L2、NFKB、NFKB1A、NGF、NKX2-1、NOTCH1、NOTCH2、NOTCH3、NPM1、NRAS、NSD1、NTRK1、NTRK2、NTRK3、NUP93、OGDH、ORC、ORC1、ORC1L、ORC1L;、ORC6L、ORCL、ORCLPCNA、PAK3、PALB2、PAPPA、PARK2、PAX、PAX3、PBRM1、PCNA、PDCD1、PDCD1LG2、PDGFRA、PDGFRB、PDHA1、PDK1、PGR、PIK3C2B、PIK3CA、PIK3CB、PIK3CG、PIK3R1、PIK3R2、PIK3RI、PKMYT、PKMYT1、PLCG2、PLK1、PMS2、POLD1、POLE、PPM1A、PPP2R1A、PREX2、PRKAR1A、PRKC1、PRKDC、PRSS8、PTCH1、PTEN、PTPN1、PTPN11、PTPRR、PTTG、PTTG1、PTTG2、PTTG3、QK1、RAC1、RAD50、RAD51、RAF1、RANBP1、RARA、RAS、RB1、RBL1、RBM10、RET、RICTOR、RIT1、RNF43、ROS1、RPTOR、RUNX1、RUNX1T1, SDHA, SDHB, SDHC, SDHD, SETD2, SF3B1, SKP2, SLAMF7, SLIT2, SMAD2, SMAD3, SMAD4, SMARCA4, SMARCB1, SMC1A, SMC1L1, SMO, SNCAIP, SOCS1, SOX10, SOX2, SOX9, SPAG1 , SPAG11A, SPAG11B, SPAG16, SPAG17, SPAG4, SPAG5, SPAG6, SPAG7, SPAG8, SPAG9, SPEN, SPOP, SPTA1, SRC, SRSF2, STAG2, STAT3, STAT4, STAT5, STAT5B, STK11, SUCLG1, SUCLG2, SUFU, SYK, T(BRACHYURY), TAF1, TBC1D8, TBX3, TERC, TERT, TERT promoter, TET2, TFDP1, TGFRB2, TNFAIP3, TNFRSF14, TOP1, TOP2A, TOP2B, TP53, TRIB3, TSC1, TSC2, TSHR, TUBB3, TYMP, TYMS, U2AF1, UNC5A, UNC5B, VEGFA, VHL, VTCN1, WEE1, WISP3, WT1, XAGE1D, XAGE2, XAGE3, XAGE5, XCL1, XCL2, XCR1, XPO1, ZBTB2, ZNF217, ZNF703, or any combination thereof.

[0108] In certain embodiments, the disclosed cancer-associated genes can comprise one or more genomic abnormalities. In certain embodiments, a subject can have one or more genomic abnormalities in the disclosed cancer-associated genes.

[0109] In some embodiments, the disclosed ALK gene can encode an ALK protein having an I1461L or N1544K mutation. In some embodiments, the disclosed ARID2 gene can encode an ARID2 protein having an N127fs18 mutation. In some embodiments, the disclosed AKT1 gene can encode an AKT1 protein having an E17K or R346H mutation. In some embodiments, the disclosed APC gene can encode an APC protein having G29G, K445K, V2716L, E918E, Q1378*, S457*, I1304fs, E888fs, R230C, Q1090Q, S1360P. In some embodiments, the disclosed gene can encode an AR protein having an A356E, M887V, or S510R mutation. In some embodiments, the disclosed ARAF gene can encode an ARAF protein having a Y495Y mutation. In some embodiments, the disclosed ARID1A gene may encode an ARID1A protein having a S1798L, S1167F, G246V, R1889W, or Q802fs mutation. In some embodiments, the disclosed ARID2 gene may encode an ARID2 protein having a N127fs18 mutation. In some embodiments, the disclosed ARTX gene has a S850fs*2 or N179fs*26 mutation. In some embodiments, the disclosed ASXL1 gene has a R1273f*s mutation. In some embodiments, the disclosed BRAF gene may encode a BRAF protein having an E264 or V600E mutation. In some embodiments, the disclosed BRCA1 gene may encode a BRAC1 protein having a H662Q or R1443* mutation. In some embodiments, the disclosed BRCA2 gene may encode a BRCA2 protein having a D237N or 12040V mutation. In certain embodiments, the disclosed CCND1 gene can encode a CCND1 protein having a R291W mutation. In certain embodiments, the disclosed CCNE1 gene can encode a CCNE1 protein having a P268P or R95Q mutation. In certain embodiments, the disclosed CDKN1B gene can encode a CDKN1B protein having a K59fs* mutation. In certain embodiments, the disclosed CDKN2A gene can encode a CDKN2A protein having a D74N mutation.In some embodiments, the disclosed CTNNB1 gene can encode a CTNNB1 protein having a T41A mutation. In some embodiments, the disclosed DDR2 gene can encode a DDR2 protein having a L749L mutation. In some embodiments, the disclosed EGFR gene can encode an EGFR protein having a P753L, V524I, D321D, or V7421 mutation. In some embodiments, the disclosed ERBB2 gene can encode an ERBB2 protein having a C584G or V797del (exon 20 deletion) mutation. In some embodiments, the disclosed EWSR1 gene can encode an EWSR1 protein having an FLI1 fusion. In some embodiments, the disclosed FBXW7 gene can encode an FBXW7 protein having a Y545C or R658* mutation. In some embodiments, the disclosed FGFR genes may encode FGFR proteins having a T320T, S726F, H791H, P47P, S430fs, or R179H mutation. In some embodiments, the disclosed FGFR1 genes may encode FGFR1 proteins having a S726F mutation. In some embodiments, the disclosed FGFR2 genes may encode FGFR2 proteins having a KCNH7 fusion. In some embodiments, the disclosed FGFR3 genes may encode FGFR3 proteins having a H290Y mutation. In some embodiments, the disclosed GATA3 genes may encode GATA3 proteins having a P433fs43, P409fs, PS405fs, D336fs, S430fs, or c.1213_1214del mutation. In some embodiments, the disclosed GNA11 genes may encode GNA11 proteins having a N244S mutation. In some embodiments, the disclosed GNAS gene can encode a GNAS protein having a R201H* mutation. In some embodiments, the disclosed HIST1H1D gene can encode a HIST1H1D protein having a K185-A186>T mutation. In some embodiments, the disclosed H3F3A gene can encode an H3F3A protein having a K28N or K27 mutation. In some embodiments, the disclosed IDH1 gene can encode an IDH1 protein having a R132H mutation.In some embodiments, the disclosed JAK2 gene can encode a JAK2 protein having a V617 mutation. In some embodiments, the disclosed KIT gene has a Q775fs (deletion of exon 16). In some embodiments, the disclosed ARID1A gene can encode an ARID1A protein having a S1798L, S1167F, G246V, R1889W, or Q802fs mutation. In some embodiments, the disclosed KRAS gene can encode a KRAS protein having a G12V, G12D, G12S, G13D, or p.AG11GD mutation. In some embodiments, the disclosed MAP2K1 gene can encode a MAP2K1 protein having a K57E mutation. In some embodiments, the disclosed MAP2K4 gene has a loss of exon 2. In some embodiments, the disclosed MAP3K1 gene can encode a MAP3K1 protein having a S398 mutation. In some embodiments, the disclosed MAP3K6 gene can encode a MAP3K6 protein having a P646L mutation. The disclosed MET gene can encode a MET protein having a C385Y, T895M, T7591, or M391 mutation. In some embodiments, the disclosed MPL gene can encode an MPL protein having a Y591D mutation. In some embodiments, the disclosed MYC gene can encode a MYC protein having a S244S mutation. In some embodiments, the disclosed NF1 gene can have splice site 480-11_4801del11, splice site SNV, c.6655>T, p.D2219Y, V2378fs*8, or encode an A2617A, F710C, I1719T, or K583R mutation. In some embodiments, the disclosed NOTCH1 gene can encode a NOTCH1 protein having an A465V, V220M, D1681H, or S223N mutation. In some embodiments, the disclosed NOTCH2 gene can encode a NOTCH2 protein having an S2379F mutation. In some embodiments, the disclosed NTRK1 gene can encode an NTRK1 protein having a P387L or R766Q mutation. In some embodiments, the disclosed PDGFRA gene can encode a PDGFRA protein having an E86A or V299G mutation.In some embodiments, the disclosed PIK3CA gene can encode a PIK3CA protein having a Q546H, Q546K, Q546R, Q597H, E542K, E545K, E726K, E39K, E453K, R4-P18del, H1047L, H104R, K567E, I15431, p.E545K, or G1049R mutation. In some embodiments, the disclosed PIK3R1 gene can encode a PIK3R1 protein having a S399Y408del splice site 917-1G>A mutation. In some embodiments, the disclosed PTCH1 has a p.M17 loss of start - LOF. In certain embodiments, the disclosed PTEN gene can encode a PTEN protein having an H196_1203DEL, R55fs, N323fs*23, Y27C, R130*, C136Y, D252Y, or a loss mutation in exons 4-7. In certain embodiments, the disclosed RAF1 gene can encode a RAF1 protein having a P63P mutation. In certain embodiments, the disclosed RB1 gene can encode a RB1 protein having a Q217*, Y173fs*, or H673fs mutation. In certain embodiments, the disclosed RUNX1 gene can encode a RUNX1 protein having an R107C mutation. In certain embodiments, the disclosed SMAD4 gene can encode a SMAD4 protein having a P511L, D537V, Q450H, L495R, A451P, or A406T mutation. In some embodiments, the disclosed SPEN gene can encode a SPEN protein having an A2510V mutation. In some embodiments, the disclosed SRSF2 gene can encode a SRSF2 protein having a P95H mutation. In some embodiments, the disclosed STAT5B gene can encode a STAT5B protein having an R110H mutation. In some embodiments, the disclosed TET2 gene can encode a TET2 protein having a C1875G mutation.In one embodiment, the disclosed TP53 gene is V73fs, R175G, R196, R249T, C176F, G187D, R282W, E287*, E285K, S241del, c.97-28_99del, Y126D, R273H, C176W, K320*, T253A, splice site 37G-1G>A, Q104, P151H, H179Y, R273C, R248W, R176H, R209fs cer, N235-Y236del, R248Q er, R306*, C176Y, S241F, L252-1254del, L145P, R158H, R213*, Y220C, R110P, V274G, or c.376-4_384del mutations.

[0110] With respect to the Guardant360 platform, the disclosed genomic abnormalities in cancer-associated genes may include single nucleotide variants. For example, in certain embodiments, the disclosed single nucleotide variants may be identified in the following genes: AKT1, ALK, APC, AR, ARAF, ATM, BRAF, BRCA1, BRCA2, CCND1, CDH1, CDK4, CDK6, CDK12, CDKN2A, CTNNB1, EGFR, ERBB2, ESR1, FGFR1, FGFR2, FGFR3, GATA3, GNA11, GNAQ, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MAP2K2, MET, MLH1, MTOR, MYC, NF1, NFE2L2, NRAS, NTRK1, NTRK3, PDGFRA, PIK3CA, PTEN, RAF1, RET, RHEB, ROS1, SMAD4, SMO, STK11, TERT, TSC1, VHL, or any combination thereof. With respect to the Guardant360 platform, the disclosed genomic abnormalities of cancer-related genes can include insertions and / or deletions. For example, in some embodiments, the disclosed indels can be identified in the following genes: AKT1, ALK, APC, ATM, BRAF, BRCA1, BRCA2, CDH1, CDK12, CDKN2A, EGFR, ERBB2, ESR1, FGFR2, GATA3, HNF1A, HRAS, KIT, KRAS, MET, MLH1, NF1, PDGFRA, PIK3CA, PTEN, RET, ROS1, STK11, TSC1, VHL, or any combination thereof. With respect to the Guardant360 platform, in some embodiments, the disclosed genomic abnormalities of cancer-related genes can include copy number amplifications (CNAs). For example, in some embodiments, the disclosed CNAs can be identified in the following genes: ERBB2 and / or MET. With respect to the Guardant360 platform, in certain embodiments, the disclosed fusions may include ALK, NTRK1, RET, ROS1, or any combination thereof.

[0111] With respect to the Foundation platform, in some embodiments, the genomic abnormalities of the disclosed cancer-associated genes can include substitutions, indels, or copy number amplifications. For example, in some embodiments, the disclosed substitutions, disclosed indels, or disclosed CNAs can be identified in the following genes: ABL1, ACVR1B, AKT1, AKT2, AKT3, ALK, ALOX12B, AMER1 (FAM723B), APC, AR, ARAF, ARFRP1, ARID1A, ASXL1, ATM, ATR, ATRX, AURKA, AURKB, AXIN1, AXL, BAP1, BARD1, BCL2, BCL2L1, BCL2L2, BCL6, BCOR, BCORL1, BRAF , BRCA1, BRCA2, BRD4, BRIP1, BTG1, BTG2, BTK, C11ORF30(EMSY), CALR, CARD11, CASP8, CBFB, CBL, CCND1, CCND2, CCND3, CCNE1, CD22, CD274( PD-L7), CD70, CD79A, CD79B, CDC73, CDH1, CDK12, CDK4, CDK6, CDK8, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, CEBPA, CHEK7, CHEK2, CIC, CRE BBP, CRKL, CSFIR, CSF3R, CTCF, CTNNA1, CTNNB1, CUL3, CUL4A, CXCR4, CYP17A1, DAXX, DDR1, DDR2, DIS3, DNMT3A, DOT1L, EED, EGFR, EP300, EP HA3, EPHB1, EPHB4, ERBB2, ERBB3, ERBB4, ERCC4, ERG, ERRFI1, ESR1, EZH2, FAM46C, FANCA, FANCC, FANCG, FANCL, FAS, FBXW7, FGF10, FGF12, FG F14, FGF19, FGF23, FGF3, FGF4, FGF6, FGFR1, FGFR2, FGFR3, FGFR4, FH, FLCN, FLT1, FLT3, FOXL2, FUBP1, GABRA6, GATA3, GATA4, GATA6, GID4( C17ORF39), GNA11, GNA13, GNAQ, GNAS, GRM3, GSK3B, H3F3A, HDAC1, HGF, HNF1A, HRAS, HSD3B1, ID3, IDH1, IDH2, IGF1R, IKBKE, IKZF1, INPP4B,<h2 style=";text-align:left;direction:ltr">IRF2, IRF4, IRS2, JAK1, JAK2, JAK3, JUN, KDM5A, KDM5C, KDM6A, KDR, KEAP1, KEL, KIT, KLHL6, KMT2A(MLL), KMT2D(MLL2), KRAS, LTK, LYN, MAF, MAP2K1 (MEK1)、MAP2K2(MEK2)、MAP2K4、MAP3K1、MAP3K13、MAPK1、MCL1、MDM2、MDM 4、MED12、MEF2B、MEN1、MERTK、MET、MITF、MKNK1、MLH1、MPL、MRE11A、MSH2、M SH3、MSH6、MST1R、MTAP、MTOR、MUTYH、MYC、MYCL(MYCL1)、MYCN、MYD88、NBN 、NF1、NF2、NFE2L2、NFKBIA、NKX2-1、NOTCH1、NOTCH2、NOTCH3、NPM1、NRAS、 NT5C2、NTRK1、NTRK2、NTRK3、P2RY8、PALB2、PARK2、PARP1、PARP2、PARP3、P AX5、PBRM1、PDCD1(PD-1)、PDCD1LG2(PD-L2)、PDGFRA、PDGFRB、PDK1、PIK3C 2B、PIK3C2G、PIK3CA、PIK3CB、PIK3R1、PIM1、PMS2、POLD1、POLE、PPARG、PP 2R1A、PPP2R2A、PRDM1、PRKAR1A、PRKCI、PTCH1、PTEN、PTPN11、PTPRO、OKI、 RAC1、RAD21、RAD51、RAD51B、RAD51C、RAD51D、RAD52、RAD54L、RAF1、RARA、 RB1、RBM10、REL、RET、RICTOR、RNF43、ROS1、RPTOR、SDHA、SDHB、SDHC、SDHD、 SETD2、SF3B1、SGK1、SMAD2、SMAD4、SMARCA4、SMARCB1、SMO、SNCAIP、SOCS1 、SOX2、SOX9、SPEN、SPOP、SRC、STAG2、STAT3、STK11、SUFU、SYK、TBX3、TEK、 TET2、TGFBR2、TIPARP、TNFAIP3、TNFRSF14、TP53、TSC1、TSC2、TYRO3、U2AF 1、VEGFA、VHL、WHSC1(MMSET)、WHSC1L1、WT1、XPO1、XRCC2、ZNF217、ZNF703、Or any combination thereof. With respect to the Foundation platform, the disclosed genomic abnormalities of cancer-related genes may include rearrangements. For example, in some embodiments, the disclosed rearrangements may be identified in the following genes: ALK, BCL2, BCR, BRAF, BRCA1, BRCA2, CD74, EGFR, ETV4, ETVS, ETV6, EWSRI, EZR, FGFR1, FGFR2, FGFR3, KIT, KMT2A (MLL), MSH2, MYB, MYC, NOTCH2, NTRKI NTRK2 NUTMI, PDGFRA, RAFT, RARA, RET, ROS1, RSPO2 SDC4, SLC34A2 TERC (ncRNA), TERT (promoter only), TMPRSS2, or any combination thereof.

[0112] With respect to the Tempus platform, in some embodiments, the genomic abnormalities of the disclosed cancer-associated genes may include rearrangements. For example, in some embodiments, the disclosed rearrangements may be identified in the following genes: ABL1, ALK, BCR, BRAF, EGFR, ETV6, EWSR1, FGFR2, FGFR3, MYB, NRG1, NTRK1, NTRK2, NTRK3, PAX8, PDGFRA, PML, RARA, RET, ROS1, TFE3, TMPRSS2, or any combination thereof. With respect to the Tempus platform, in some embodiments, the genomic abnormalities of the disclosed cancer-associated genes may include single-nucleotide variants, indels, or copy number amplifications. For example, in certain embodiments, the disclosed single nucleotide variants, disclosed indels, or disclosed CNAs may be identified in the following genes: ABCB1, ABCC3, ABL1, ABL2, ABRAXAS1, ACTA2, ACVR1, (ALK2), ACVR1B, AGO1, AJUBA, AKT1, AKT2, AKT3, ALK, AMER1, APC, APLNR, APOB, AR, ARAF, ARHGAP26, ARHGAP35, ARID1A, ARID1B, ARID2, ARID5B, ASNS, ASPSCR1, ASXL1, ATIC, ATM, ATP7B, ATR, ATRX, AURKA, AURKB, AXIN1, AXIN2, AXL, B2M, BAP1, BARD1, BCL10, BCL11B, BCL2, BCL2L1, BCL2L11, BCL6, BCL7A, BCLAF1, BCOR, BCORL1, BCR, BIRC3, BLM, BMPR1A, BRAF, BRCA1, BRCA2, BRD4, BRIP1, BTG1, BTK, BUB1 B, C11orf65, C3orf70, C8orf34, CALR, CARD11, CARM1, CASP8, CASR, CBFB, CBL, CBLB, CBLC, CBR3, CCDC6, C CND1, CCND2, CCND3, CCNE1, CD19, CD22, CD274, (PD-L1), CD40, CD70, CD79A, CD79B, CDC73, CDH1, CDK12, C DK4, CDK6, CDK8, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CEBPA, CEP57, CFTR, CHD2, CHD4, CHD7,CHEK1, CHEK2, CIC, CIITA, CKS1B, CREBBP, CRKL, CRLF2, CSF1R, CSF3R, CTC1 CTCF, CTLA4, CTNNA1, CTNNB1, CTRC, CUL1, CUL3, CUL4A, CUL4B, CUX1, CXCR 4. CYLD, CYP1B1, CYP2D6, CYP3A5, CYSLTR2, DAXX, DDB2, DDR2, DDX3X, DICER 1, DIRC2, DIS3, DIS3L2, DKC1, DNM2, DNMT3A, DOT1L, DPYD, DYN, C2H1, EBF1, E CT2L, EGF, EGFR, EGLN1, EIF1AX, ELF3, ELOC, (TCEB1), EMSY, ENG, EP300, EP CAM, EPHA2, EPHA7, EPHB1, EPHB2, EPOR, ERBB2 (HER2), ERBB3, ERBB4, ERCC1 ERCC2, ERCC3, ERCC4, ERCC5, ERCC6, ERG, ERRFI1, ESR1, ETS1, ETS2, ETV1 ETV4, ETV5, ETV6, EWSR1, EZH2, FAM46C, FANCA, FANCB, FANCC, FANCD2, FANCE FANCF, FANCG, FANCI, FANCL, FANCM, FAS, FAT1, FBXO11, FBXW7, FCGR2A, FC GR3A, FDPS, FGF1, FGF10, FGF14, FGF2, FGF23, FGF3, FGF4, FGF5, FGF6, FGF7 FGF8, FGF9, FGFR1, FGFR2, FGFR3, FGFR4, FH, FHIT, FLCN, FLT1, FLT3, FLT4 FNTB, FOXA1, FOXL2, FOXO1, FOXO3, FOX, P1, FOXQ1, FRS2, FUBP1, FUSG6PD, GA BRA6、GALNT12、GATA1、GATA2、GATA3、GATA4、GATA6、GEN1、GLI1、GLI2、GNA1 1, GNA13, GNAQ, GNAS, GPC3, GPS2, GREM1, GRIN2A, GRM3, GSTP1, H19, H3F3A, H AS3, HAVCR2, HDAC1, HDAC2, HDAC4, HGF, HIF1A, HIST1H1E, HIST1H3B, HIST1 H4E、SON-A、SON-B、SON-C、SON-DMA、SON-DMB、SON-DOA、SON-DOB、SON-DPA1<h2 style=";text-align:left;direction:ltr">HLA-DPB1, HLA-DPB2, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB5, HLA-DRB6, HLA-E, HLA-F, HLA-G, HNF1A, HNF1B, HOXA1 1, HOXB13, HRAS, HSD11B2, HSD3B1, HSD3B2, HSP90AA1, HSPH1, IDH1, IDH2, IDO1, IFIT1, IFIT2, IFIT3, IFNAR1, IFNAR2, IFNGR1, IFNGR2, IFNL3, IKBKE, I KZF1, IL10RA, IL15, IL2RA, IL6R, IL7R, ING1, INPP4B, IRF1, IRF2, IRF4, IRS2, ITPKB, JAK1, JAK2, JAK3, JUN, KAT6A, KDM5A, KDM5C, KDM5D, KDM6A, KDR, K EAP1、KEL、KIF1B、KIT、KLF4、KLHL6、KLLN、KMT2A、KMT2B、KMT2C、KMT2D、KRA S、L2HGDH、LAG3、LATS1、LCK、LDLR、LEF1、LMNA、LMO1、LRP1B、LYN、LZTR1、MAD 2L2、MAF、MAFB、MAGI2、MALT1、MAP2K1、MAP2K2、MAP2K4、MAP3K1、MAP3K7、MA PK1、MAX、MC1R、MCL1、MDM2、MDM4、MED12、MEF2B、MEN1、MET、MGMT、MIB1、MITF 、MKI67、MLH1、MLH3、MLLT3、MN1、MPL、MRE11、MS4A1、MSH2、MSH3、MSH6、MTAP 、MTFD2、MTHFR、MTOR、MTRR、MUTYH、MYB、MYC、MYCL、MYCN、MYD88、MYH11、NBN 、NCOR1、NCOR2、NF1、NF2、NFE2L2、NFKBIA、NHP2、NKX2-1、NOP10、NOTCH1、NO TCH2、NOTCH3、NOTCH4、NPM1、NQO1、NRAS、NRG1、NSD1、NSD2、NT5C2、NTH、L1、N TRK1、NTRK2、NTRK3、NUDT15、NUP98、OLIG2、P2RY8、PAK1、PALB2、PALLD、PAX 3、PAX5、PAX7、PAX8、PBRM1、PCBP1、PDCD1、PDCD1LG2、PDGFRA、PDGFRB、PDK1、<h2 style=";text-align:left;direction:ltr">PHF6、PHGDH、PHLPP1、PHLPP2、PHOX2B、PIAS4、PIK3C2B、PI、K3、CA、PIK3CB、 PI、K3、CD、PIK3CG、PI、K3、R1、PIK3R2、PIM1、PLCG1、PLCG2、PML、PMS1、PMS2 、POLD1、POLE、POLH、POLQ、POT1、POU2F2、PPARA、PPARD、PPARG、PPM1D、PPP1 R15A、PPP2R1A、PPP2R2A、PPP6C、PRCC、PRDM1、PREX2、PRKAR1A、PRKDC、PRKN、 PRSS1、PTC、H、1、PTCH2、PTEN、PTPN11、PTPN13、PTPN22、PTPRD、PTPRT、QKI、 RAC1、RAD21、RAD50、RAD51、RAD51B、RAD51C、RAD51D、RAD54L、RAF1、RANBP2 、RARA、RASA1、RB1、RBM10、RECQL4、RET、RHEB、RHOA、RICTOR、RINT1、RIT1、R NF139、RNF43、ROS1、RPL5、RPS15、RPS6KB1、RPTOR、RRM1、RSF1、RUNX1、、RUNX 1T1, RXRA, SCG5, SDHA, SDHAF2, SDHB, SDHC, SDHD, SEC23B, SEMA3C, SETBP1, SETD2, SF3B1, SGK1, SH2B3, SHH, SLC26A3, SLC47A2, SLC9A3R1, SLIT2, SLX4 、SM、AD2、SMAD3、SMAD4、SMARCA1、SMARCA4、SMARCB1、SMARCE1、SMC1A、SMC3 、SMO、SOCS1、SOD2、SOX10、SOX2、SOX9、SPEN、SPINK1、SPOP、SPRED1、SRC、SRS F2, STAG2, STAT3, STAT4, STAT5A, STAT5B, STAT6, STK11, SUFU, SUZ12, SYK, SYNE1, TAF1, TANC1, TAP1, TAP2, TARBP2, TBC1D12, TBL1XR1, TBX3, TCF3, TCF 7L2、TCL1A、TERT(プロモーター)、TET2、TFE3、TFEB、TFEC、TGFBR1、TGFBR2、TIGIT 、TMEM127、TMEM173、TMPRSS2、TNF、TNFAIP3、TNFRSF14、TNFRSF17、TNFRSF9、TOP1, TOP2A, TP53, TP63, TPM1, TPMT, TRAF3, TRAF7, TSC1, TSC2, TSHR, TUSC3, TYMS, U2AF1, UBE2T, UGT1A1, UGT1A9, UMPS, VEGFA, VEGFB, VHL, VSIR, WEE1, WNK1, WNK2, WRN, WT1, XPA, XPC, XPO1, XRCC1, XRCC2, XRCC3, YEATS4, ZFHX3, ZMYM3, ZNF217, ZNF471, ZNF620, ZNF750, ZNRF3, ZRSR2, or any combination thereof.

[0113] For the Tempus platform, the following apply: APC (APC-associated conditions), ATM (Ataxia-telangiectasia, breast cancer susceptibility, pancreatic cancer susceptibility), AXIN2 (oligodontia-colorectal cancer syndrome), BAP1 (BAP1 tumor predisposition syndrome), BARD1 (breast cancer susceptibility), BLM (Bloom syndrome), BMPR1A (juvenile polyposis), BRCA1 (hereditary breast and ovarian cancer), BRCA2 (hereditary breast and ovarian cancer, Fanconi anemia), BRIP1 (ovarian cancer susceptibility, Fanconi anemia), CDH1 (hereditary gastric cancer), breast cancer susceptibility), CDK4 (melanoma susceptibility), CDKN2A (melanoma-pancreatic cancer syndrome), CEBPA (acute myeloid leukemia susceptibility), CHEK2 (breast cancer susceptibility, colon cancer susceptibility), DICER1 (DICER1 tumor predisposition syndrome), EGFR (lung cancer susceptibility, TKI resistance), EPCAM (Lynch syndrome), ETV6 (leukemia susceptibility, thrombocytopenia susceptibility), F H (hereditary leiomyomatosis and renal cell carcinoma), FLCN (Birt-Hogg-Dubé syndrome), GATA2 (GATA2 deficiency with susceptibility to myeloid malignancies), KIT (familial gastrointestinal stromal tumors), MAX (hereditary paraganglioma-pheochromocytoma syndrome), MEN1 (multiple endocrine neoplasia type 1), MET (hereditary papillary renal cell carcinoma), MLH1 (Lynch syndrome, constitutional mismatch repair deficiency), MSH2( Lynch syndrome, constitutional mismatch repair deficiency), MSH3 (MSH3-associated polyposis), MSH6 (Lynch syndrome, constitutional mismatch repair deficiency), MUTYH (MUTYH-associated polyposis), NBN (Nijmegen chromosomal instability syndrome, breast cancer susceptibility), NF1 (neurofibromatosis type 1), NF2 (neurofibromatosis type 2), NTHL1 (NTHL1 tumor syndrome, NTHL1-associated polyposis), PALB2 (breast cancer susceptibility, pancreatic cancer susceptibility, ovarian cancer susceptibility, Fanconi anemia), PDGFRA (familial gastrointestinal stromal tumor, GIST-plus syndrome), PHOX2B (neuroblastoma susceptibility), PMS2 (Lynch syndrome, constitutional mismatch repair deficiency), POLD1 (polymerase proofreading-associated polyposis), POLE (polymerase proofreading-associated polyposis), PRKAR1A (Carney complex),PTCH1 (Gorlin syndrome, basal cell nevus syndrome), PTEN (PTEN hamartoma tumor syndrome), RAD51C (ovarian cancer susceptibility, breast cancer susceptibility, Fanconi anemia), RAD51D (ovarian cancer susceptibility, breast cancer susceptibility), RB1 (retinoblastoma), RET (multiple endocrine neoplasia type 2, familial medullary thyroid carcinoma), RUNX1 (acute myeloid leukemia susceptibility), SDHA (hereditary paraganglioma-pheochromocytoma syndrome), SDHAF2 (hereditary paraganglioma-pheochromocytoma syndrome), SDHB (hereditary paraganglioma-pheochromocytoma syndrome), SDHC (hereditary paraganglioma-pheochromocytoma syndrome) , SDHD (hereditary paraganglioma-pheochromocytoma syndrome), SMAD4 (juvenile polyposis, hereditary hemorrhagic telangiectasia), SMARCA4 (rhabdoid tumor predisposition syndrome), SMARCB1 (rhabdoid tumor predisposition syndrome, schwannomatosis), STK11 (Peutz-Jeghers syndrome), SUFU (Gorlin syndrome, basal cell nevus syndrome), TMEM127 (hereditary paraganglioma-pheochromocytoma syndrome), TP53 (Li-Fraumeni syndrome), TSC1 (tuberous sclerosis complex), TSC2 (tuberous sclerosis complex), VHL (von Hippel-Lindau disease), and WT1 (WT1-associated Wilms tumor).

[0114] In some embodiments of the disclosed methods for treating and / or preventing cancer, next-generation sequencing can comprise sequencing one or more cancer-related genes.In some embodiments of the disclosed methods for treating and / or preventing cancer, sequencing one or more cancer-related genes can comprise identifying one or more genomic abnormalities.In some embodiments, one or more genomic abnormalities can comprise somatic genomic abnormalities.In some embodiments, the one or more disclosed somatic genomic abnormalities can comprise mutation, insertion, deletion, chromosome rearrangement, copy number abnormality, or any combination thereof.

[0115] In some embodiments of the disclosed methods for treating and / or preventing cancer, the disclosed cfDNA analysis can include quantifying one or more cancer-related genes.In some embodiments, if the expression and / or amount and / or presence of one or more disclosed genomic abnormalities in biological samples before treatment is greater than the expression and / or amount and / or presence of the same one or more genomic abnormalities in control samples, the disclosed methods for treating and / or preventing cancer can include diagnosing the subject as needing high-precision cancer treatment.In some embodiments, the disclosed control sample can be a sample obtained from a subject without cancer.In some embodiments, the disclosed control sample can be a pooled sample obtained from more than one subject without cancer.

[0116] In certain embodiments, if the expression and / or amount and / or presence of one or more disclosed genomic abnormalities in a post-treatment biological sample is less than the expression and / or amount and / or presence of the same one or more genomic abnormalities in a pre-treatment sample, the disclosed methods of treating and / or preventing cancer can include continuing to administer a disclosed high-precision cancer treatment to the subject. In certain embodiments, if the expression and / or amount and / or presence of one or more disclosed genomic abnormalities in a post-treatment biological sample is less than the expression and / or amount and / or presence of the same one or more genomic abnormalities in a previous post-treatment sample, the disclosed methods of treating and / or preventing cancer can include continuing to administer a disclosed high-precision cancer treatment to the subject.

[0117] In certain embodiments, the disclosed methods of treating and / or preventing cancer may further include measuring the subject's tumor response to the high-precision cancer treatment. In certain embodiments, the subject's tumor response may include a partial response or a complete response. In certain embodiments, the disclosed partial response may include a 25% or greater reduction in tumor size or one or more tumors compared to the same tumor size or the same tumor(s) before treatment. In certain embodiments, the disclosed partial response may include a 50% or greater reduction in tumor size or one or more tumors compared to the same tumor size or the same tumor(s) before treatment. In certain embodiments, the disclosed partial response may include a 100% or greater reduction in tumor size or one or more tumors compared to the same tumor size or the same tumor(s) before treatment.

[0118] In certain embodiments, the disclosed methods for treating and / or preventing cancer may further comprise measuring a subject's molecular response to a disclosed high-precision cancer treatment. In certain embodiments, the disclosed molecular response may comprise a reduction in the number of somatic genomic abnormalities in a disclosed biological sample obtained from the subject. In certain embodiments, the disclosed somatic genomic abnormalities may comprise mutations, insertions, deletions, chromosomal rearrangements, copy number abnormalities, fusions, or any combination thereof. In certain embodiments, the disclosed methods for treating and / or preventing cancer may further comprise administering one or more additional therapeutic agents to the subject.

[0119] In certain aspects, the disclosed additional therapeutic agents can include a chemotherapeutic agent, a monoclonal antibody, a cell cycle inhibitor, a small molecule, or any combination thereof.

[0120] Monoclonal antibodies are known to those skilled in the art and may include, but are not limited to, adotrastuzumab, alemtuzumab, atezolizumab, avelumab, bevacizumab, blinatumomab, brentuximab, cemiplimab, cetuximab, daratumumab, denosumab, dinutuximab, durvalumab, elotuzumab, gemtuzumab, ibritumomab, inotuzumab, ipilimumab, necitumumab, nivolumab, obinutuzumab, ofatumumab, olaratumumab, panitumumab, pembrolizumab, pertuzumab, ramucirumab, rituximab, tositumomab, trastuzumab, or any combination thereof.

[0121] Small molecules are known to those skilled in the art. Examples of small molecules include abemaciclib, afatinib, alectinib, alpelisib, axitinib, binimetinib, bosutinib, brigatinib, cabozantinib, carfilzomib, ceritinib, gilteritinib (cgilteritinib), cobimetinib, copanlisib, crizotinib, dabrafenib, dacomitinib, dasatinib, duvelisib, encorafenib, entrectinib, erdafitinib, erlotinib, gefitinib, and ibromidine. These may include, but are not limited to, rutinib, imatinib, ivosidenib, lapatinib, larotrectinib, lenvatinib, lorlatinib, marizomib, neratinib, nilotinib, niraparib, olaparib, osimertinib, palbociclib, pazopanib, ponatinib, regorafenib, ribociclib, rucaparib, sorafenib, sunitinib, talazoparib, trametinib, vandetanib, vemurafenib, or any combination thereof. In some embodiments, the additional therapeutic agent may include bevacizumab, pazopanib, sorafenib, dasatinib, everolimus, or any combination thereof.

[0122] For example, in some embodiments, pazopanib and / or sorafenib can be orally administered to a subject at a dose of about 1 mg / kg / day to about 12 mg / kg / day, or 2 mg / kg / day to about 6 mg / kg / day. In some embodiments, the disclosed optimal dose of pazopanib and / or sorafenib can be about 3 mg / kg / day. In some embodiments, dasatinib can be orally administered to a subject at a dose of about 0.3 mg / kg / day to about 2.0 mg / kg / day, or about 0.7 mg / kg / day to about 1.4 mg / kg / day. In some embodiments, the disclosed optimal dose of dasatinib can be about 0.7 mg / kg / day. In some embodiments, everolimus can be orally administered to a subject at a dose of about 0.03 mg / kg / day to about 0.15 mg / kg / day, or about 0.03 mg / kg / day to about 0.10 mg / kg / day. In some embodiments, the disclosed optimal dose of everolimus can be about 0.07 mg / kg / day. In some embodiments, bevacizumab can be administered intravenously to a subject at a dose of about 2 mg / kg / day to about 15 mg / kg / day every 1-3 weeks, or at a dose of about 5 mg / kg / day to about 12 mg / kg / day every 1-3 weeks. In some embodiments, the disclosed optimal dose of bevacizumab can be administered intravenously to a subject at an optimal dose of about 10 mg / kg / day every 2 weeks.

[0123] In certain embodiments, the disclosed molecular markers that may determine one or more appropriate high-precision cancer treatments in one or more disclosed methods can be measured from a sample by high-density expression arrays, DNA microarrays, polymerase chain reaction (PCR), reverse transcriptase PCR (RT-PCR), real-time quantitative reverse transcription PCR (qRT-PCR), serial analysis of gene expression (SAGE), spotted cDNA arrays, GeneChips, spotted oligo arrays, bead arrays, RNA-Seq, tiling arrays, Northern blotting, hybridization microarrays, in situ hybridization, whole exome sequencing, whole genome sequencing, liquid biopsy, next-generation sequencing, or any combination thereof.

[0124] In some embodiments, the disclosed molecular markers can determine one or more suitable high-precision cancer treatments for use in the disclosed methods for treating and / or preventing cancer, and can be determined from at least one nucleic acid sequence of circulating DNA and / or RNA. In some embodiments, the disclosed molecular markers can be evaluated from circulating tumor DNA and / or RNA (ctDNA and / or ctRNA); circulating cell-free DNA and / or RNA (cfDNA, cfRNA); or any combination thereof. ctDNA / ctRNA refers to fragmented DNA derived from tumors in the bloodstream that is not associated with cells. cfDNA / cfRNA refers to DNA that circulates freely in the bloodstream but does not necessarily originate from tumors. In some embodiments, cfDNA / ctDNA can include any whole or fragmented genomic DNA or mitochondrial DNA, and / or cfRNA / ctRNA can include mRNA, tRNA, microRNA, small interfering RNA, and long non-coding RNA (ncRNA). In some embodiments, cfDNA and / or ctDNA can be fragmented DNA with a length of at least about 50 base pairs (bp), about 100bp, about 200bp, about 500bp, or about 1 kbp. In some embodiments, cfRNA and / or ctRNA can be full-length or fragments of mRNA (e.g., at least 70% of full length, at least 50% of full length, at least 30% of full length, etc.). In some embodiments, the disclosed molecular markers can be targeted to any cancer-related gene disclosed herein.

[0125] In certain aspects, the disclosed methods may further include surgically removing one or more tumors from the subject. In certain aspects, the disclosed methods may further include repeating one or more of the disclosed steps of the disclosed methods.

[0126] For example, in certain aspects, repeating one or more disclosed steps of the disclosed methods can include repeating administering a precision cancer treatment to the subject, repeating measuring the subject's tumor response, repeating obtaining a biological sample from the subject, repeating subjecting the biological sample to cfDNA analysis, repeating administering one or more additional therapeutic agents, or any combination thereof.

[0127] In certain embodiments, the disclosed molecular markers can be detected, quantified, and / or analyzed over time (at various time points) to determine the effect of the disclosed precision cancer treatments (e.g., AS treatment) on a subject and / or to determine the response of the subject or the subject's tumor to the precision cancer treatment (e.g., development of resistance, susceptibility, etc.). In certain embodiments, the disclosed methods can include obtaining multiple measurements from the same subject over time, and the same sample can be quantified at a single time point or over time. In certain embodiments, treatment with the disclosed treatment regimens (e.g., the disclosed precision cancer treatments comprising one or more antineoplastons) can be designed and / or determined based on the state of the cancer and / or the alteration / type of one or more molecular markers. In certain embodiments, the likelihood of success of the disclosed precision cancer treatments can be determined based on the state of the cancer and the type / quantity of one or more molecular markers.

[0128] In some embodiments, the disclosed molecular markers may be derived from genes expressed in one or more cells of a tumor or in immune cells, and may indicate an immunosuppressive tumor microenvironment, the occurrence of cancer stemness, the onset of metastasis, the state of cancer, or any combination thereof. In some embodiments, the disclosed molecular markers may be proteins or peptides encoded by the genes from which the molecular markers are derived, and can be targeted by antagonists or any other type of binding molecules to inhibit the function of the peptides.

[0129] Thus, in certain embodiments, increased expression (e.g., above a predetermined threshold) of the disclosed molecular markers derived from the disclosed genes associated with an immunosuppressive tumor microenvironment can be associated with the presence of an immunosuppressive tumor microenvironment, and can be associated with the fact that antagonists against peptides encoded by genes associated with an immunosuppressive tumor microenvironment may have a high probability of success in inhibiting the immunosuppressive tumor microenvironment and further promoting immune cell activity against tumor cells within such a microenvironment, thereby inhibiting cancer progression. In certain embodiments, once a molecular marker is identified, any appropriate antagonist against the target gene or protein product can be used. For example, in certain embodiments, a specific kinase can be targeted by a kinase inhibitor, or a specific signaling receptor can be targeted by a synthetic ligand, or a specific checkpoint receptor can be targeted by a synthetic antagonist or antibody, etc. In certain embodiments, the disclosed antagonists against the target molecules herein can be administered before, after, or in combination with AS treatment.

[0130] In some embodiments, the subject may be a human patient. In some embodiments, the subject may be of any age (e.g., elderly, adult, young adult, teenager, tween, adolescent, child, toddler, infant, or newborn), male or female, of any nationality, any ethnicity, and / or any race. In some embodiments, the subject may have terminal cancer.

[0131] In some aspects, the disclosed subject has not received treatment prior to administration of the disclosed precision cancer treatment. In some aspects, the disclosed subject has received treatment prior to administration of the disclosed precision cancer treatment. In some aspects of the disclosed methods, the subject has received surgery, antibody treatment, chemotherapy treatment, radiation treatment, immunotherapy treatment, or any combination thereof prior to administration of the disclosed precision cancer treatment. In some aspects of the disclosed methods, the subject in need thereof has been diagnosed with cancer, or the subject in need thereof is suspected of having cancer.

[0132] In certain embodiments, the disclosed cancers may be refractory cancers or refractory diseases. In certain embodiments, "refractory" refers to cancers and / or tumors that do not respond to treatment and / or become resistant to treatment. In certain embodiments, the subject may have relapsed disease. In certain embodiments, "relapsed" or "relapse" refers to a tumor that returns or progresses after a period of improvement with treatment (e.g., partial or complete response). In certain embodiments, the disclosed cancers may include solid tumors. In certain embodiments, the disclosed cancers may include metastatic cancers. In certain embodiments, the disclosed cancers may include terminal cancers.

[0133] In certain embodiments, the disclosed cancers include adenocarcinomas (including those of the adnexa and cervix), adenoid cystic carcinoma, adult T-cell leukemia, anaplastic astrocytoma, anaplastic ependymoma, anaplastic oligodendroglioma, astrocytoma, basal cell carcinoma, B-cell carcinoma, benign and malignant lymphoma, biliary tract-cholangiocarcinoma, intestine, brain cancers (anaplastic astrocytoma, anaplastic ependymoma, anaplastic oligodendroglioma, brainstem anaplastic astrocytoma, brainstem glioma, diffuse astrocytoma, DIPG, h3k27 mutation, ganglioglioma, glioblastoma multiforme, medulloblastoma, pilocytic astrocytoma, brainstem glioma), breast cancer, Burkitt's lymphoma, bladder cancer and bladder cancer, carcinoma of unknown primary, carcinosarcoma, cervical cancer, cholangiocarcinoma, chronic atypical myeloid leukemia, chronic atypical myeloid leukemia, colon cancer, colorectal cancer, diffuse astrocytoma, diffuse intrinsic pontine glioma (DIPG), uterine cancer, endometrial cancer, ependymoma, esophageal cancer and esophageal cancer, euthyroid Ing's sarcoma, ganglioglioma, ganglioneuroma, gastrointestinal stromal tumor (gist), glioblastoma, glioma, head and neck cancer, angiosarcoma, hepatocellular carcinoma, renal cell carcinoma, Hodgkin's disease, Kaposi's sarcoma, kidney cancer and renal carcinoma, large B-cell lymphoma, leptomeningeal carcinomatosis, leukemia, liposarcoma, liver cancer, lung cancer (non-small cell and small cell carcinoma), medulloblastoma, melanoma, meningeal sarcoma, meningioma, multiple myeloma, myelodysplastic syndrome, myeloproliferative disorders, muscle tumor, neuroblastoma, neuroendocrine carcinoma, neurofibroma, non-Hodgkin's lymphoma, oligodendroglioma, osteosarcoma, ovarian cancer and ovarian cancer, pancreatic cancer and pancreatic cancer, peripheral neuroepithelioma, peripheral T-cell lymphoma, Philadelphia chromosome positive ALL and positive CML, pilocytic astrocytoma, pineal cell tumor, pleomorphic sarcoma, pre-B cell lymphoma, primitive neuroectodermal tumor (PNET), prostate cancer and prostate cancer, refractory anemia, salivary gland cancer, sarcoma tumors, schwannoma, skin cancer and skin cancer, squamous cell carcinoma, gastric cancer and gastric cancer, synovial sarcoma, testicular cancer, thyroid cancer and thyroid cancer, T-lineage acute lymphoblastic leukemia (T-all), T-lineage lymphoblastic lymphoma (T-LL), urothelial cancer and high-grade urothelial carcinoma, uterine cancer, cervical cancer, vulvar cancer, and / or endometrial cancer, Wilms' tumor or teratocarcinoma, or any combination thereof.

[0134] In certain aspects, the disclosed cancers include breast cancer, colorectal cancer, head and neck cancer, kidney cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, brain cancer, adenoid cystic carcinoma, anaplastic astrocytoma, anaplastic ependymoma, anaplastic oligodendroglioma, brain stem glioma, diffuse astrocytoma, diffuse intrinsic pontine glioma (DIPG), ganglioglioma, medulloblastoma, pilocytic astrocytoma, cholangiocarcinoma, chronic atypical myeloid leukemia, endometrial cancer, esophageal cancer, Ewing's sarcoma, gastrointestinal stromal tumor (GIST), leptomeningeal carcinomatosis, multiple myeloma, myelodysplastic syndrome, neuroendocrine carcinoma, non-Hodgkin's lymphoma, pleomorphic sarcoma, primitive neuroectodermal tumor (PNET), refractory anemia, salivary gland cancer, skin cancer, stomach cancer, The cancers may include thyroid cancer, urothelial cancer, or any combination thereof.

[0135] In certain aspects, the disclosed methods may further include monitoring the subject for adverse effects (e.g., liver dysfunction, hematologic toxicity, neurotoxicity, skin toxicity, gastrointestinal toxicity, or any combination thereof). In certain aspects, in the absence of adverse effects, the disclosed methods may further include continuing to administer the disclosed high-precision cancer treatment to the subject. In certain aspects, in the presence of adverse effects, the disclosed methods may further include modifying one or more disclosed steps of the disclosed methods. In certain aspects, the disclosed methods may further include treating one or more adverse effects.

[0136] In certain aspects, the disclosed methods can include modifying the disclosed administering step. In certain aspects, the disclosed administering step can include changing the amount of one or more antineoplastons or compositions comprising one or more antineoplastons administered to the subject, changing the frequency with which one or more antineoplastons or compositions comprising one or more antineoplastons are administered to the subject, changing the duration of administration of one or more antineoplastons or compositions comprising one or more antineoplastons, changing the route of administration of one or more antineoplastons or compositions comprising one or more antineoplastons administered to the subject, or any combination thereof.

[0137] In some embodiments, the disclosed methods may further include obtaining a tissue biopsy from the subject. In some embodiments, the disclosed tissue biopsy can be subjected to next-generation sequencing. In some embodiments, the disclosed methods may include subjecting the subject to one or more invasive or non-invasive diagnostic evaluations. Diagnostic evaluations are known in the art. In some embodiments, the disclosed non-invasive diagnostic evaluations may include X-rays, computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, ultrasound, positron emission tomography (PET) scans, or any combination thereof. In some embodiments, the disclosed invasive diagnostic evaluations may include tissue biopsies or exploratory surgery.

[0138] In some embodiments, the disclosed subject can have improved life expectancy. In some embodiments, the subject's life expectancy is compared with the life expectancy of a control. In some embodiments, the control is a subject who has not undergone high-precision cancer treatment. In some embodiments, the control is a pooled number of subjects who have not undergone high-precision cancer treatment. In some embodiments, the control is one or more subjects with the same type and stage of cancer as the subject. In some embodiments of the disclosed method for extending the survival of a subject, the subject's cancer is treated.

[0139] In certain embodiments, the disclosed methods may improve life expectancy compared to the life expectancy from cancer of an untreated subject with the same or nearly the same disease state and the same or nearly the same predicted outcome. As used herein, "life expectancy" is defined as the point at which 50 percent of subjects are alive and 50 percent are dead. In certain embodiments, a patient's life expectancy after treatment with the disclosed methods may be indefinite. In certain embodiments, a patient's life expectancy may be extended by at least about 5% or more to at least about 100%, by at least about 10% or more to at least about 95% or more, by at least about 20% or more to at least about 80% or more, or by at least about 40% or more to at least about 60% or more compared to an untreated subject with the same or nearly the same disease state and the same or nearly the same predicted outcome.

[0140] In certain embodiments, life expectancy may be increased by at least about 5% or more, at least about 10% or more, at least about 15% or more, at least about 20% or more, at least about 25% or more, at least about 30% or more, at least about 35% or more, at least about 40% or more, at least about 45% or more, at least about 50% or more, at least about 55% or more, at least about 60% or more, at least about 65% or more, at least about 70% or more, at least about 75% or more, at least about 80% or more, at least about 85% or more, at least about 90% or more, at least about 95% or more, or at least about 100% compared to an untreated subject with the same or approximately the same disease state and the same or approximately the same predicted outcome.In certain embodiments, life expectancy is at least about 5% or more to at least about 10% or more, at least about 10% or more to at least about 15% or more, at least about 15% or more to at least about 20% or more, at least about 20% or more to at least about 25% or more, at least about 25% or more to at least about 30% or more, at least about 30% or more to at least about 35% or more, at least about 35% or more to at least about 40% or more, at least about 40% or more to at least about 45% or more, at least about 45% or more to at least about 50% or more, compared to untreated patients with the same or nearly the same disease state and the same or nearly the same predicted outcome. % or more, at least about 50% or more to at least about 55% or more, at least about 55% or more to at least about 60% or more, at least about 60% or more to at least about 65% or more, at least about 65% or more to at least about 70% or more, at least about 70% or more to at least about 75% or more, at least about 75% or more to at least about 80% or more, at least about 80% or more to at least about 85% or more, at least about 85% or more to at least about 90% or more, at least about 90% or more to at least about 95% or more, at least about 95% or more to at least about 100% extended.

[0141] In some embodiments, the disclosed methods may include protecting a subject from metastasis. In some embodiments, the disclosed methods may include reducing the risk of developing metastasis. In some embodiments of the disclosed methods, treating cancer may include increasing the subject's chance of survival, increasing the length of time before metastasis, reducing the possibility of surgical intervention, reducing the need to administer one or more additional therapeutic agents or regimens, reducing the size of one or more tumors in a subject, eliminating one or more tumors in a subject, reducing or eliminating the prevalence of one or more genomic abnormalities, restoring normal metabolism in one or more organ systems in a subject, restoring one or more aspects of cellular homeostasis and / or cellular functionality, and / or metabolic dysregulation, or any combination thereof.

[0142] In certain embodiments of the disclosed methods, restoring one or more aspects of cellular homeostasis and / or cellular functionality may include one or more of the following: (i) correcting cellular starvation in one or more cell types (e.g., hepatocytes and muscle cells, etc.); (ii) normalizing aspects of the autophagy pathway (e.g., correcting, preventing, reducing, and / or reversing autophagy, etc.); (iii) improving, enhancing, restoring, and / or preserving mitochondrial functionality and / or structural integrity; (iv) organelle functionality and / or structural integrity; (v) preventing, slowing, and / or eliminating hypoglycemia, ketosis, and / or other liver abnormalities, (vi) correcting liver enzyme dysregulation, (vii) reversing, inhibiting, preventing, stabilizing, and / or slowing tumor metastasis, (viii) reversing, inhibiting, preventing, stabilizing, and / or slowing tumor growth and / or cancer spread, or (ix) any combination thereof. In certain embodiments, restoring one or more aspects of cellular homeostasis can include, for example, improving, enhancing, restoring, and / or preserving one or more aspects of the structural and / or functional integrity of cells in an organ or system affected by cancer.

[0143] For example, in certain embodiments, tumor growth may be reduced by at least about 5% or more to at least about 100%, at least about 10% or more to at least about 95% or more, at least about 20% or more to at least about 80% or more, at least about 40% or more to at least about 60% or more, compared to an untreated subject with the same or nearly the same disease state and the same or nearly the same predicted outcome. In certain embodiments, one or more tumors in a subject treated using the disclosed methods may grow at least 5% (or more, as described above) less than an untreated subject with the same or nearly the same disease state and the same or nearly the same predicted outcome.

[0144] In certain embodiments, tumor growth may be reduced by at least about 5% or more, at least about 10% or more, at least about 15% or more, at least about 20% or more, at least about 25% or more, at least about 30% or more, at least about 35% or more, at least about 40% or more, at least about 45% or more, at least about 50% or more, at least about 55% or more, at least about 60% or more, at least about 65% or more, at least about 70% or more, at least about 75% or more, at least about 80% or more, at least about 85% or more, at least about 90% or more, at least about 95% or more, or at least about 100% compared to an untreated subject with the same or approximately the same disease state and the same or approximately the same predicted outcome.

[0145] In certain embodiments, tumor growth is at least about 5% or more to at least about 10% or more, at least about 10% or more to at least about 15% or more, at least about 15% or more to at least about 20% or more, at least about 20% or more to at least about 25% or more, at least about 25% or more to at least about 30% or more, at least about 30% or more to at least about 35% or more, at least about 35% or more to at least about 40% or more, at least about 40% or more to at least about 45% or more, at least about 45% or more to at least about 50% or more, or It may be reduced by 0% or more, at least about 50% or more to at least about 55% or more, at least about 55% or more to at least about 60% or more, at least about 60% or more to at least about 65% or more, at least about 65% or more to at least about 70% or more, at least about 70% or more to at least about 75% or more, at least about 75% or more to at least about 80% or more, at least about 80% or more to at least about 85% or more, at least about 85% or more to at least about 90% or more, at least about 90% or more to at least about 95% or more, at least about 95% or more to at least about 100%.

[0146] In certain embodiments, treatment of a tumor according to the methods disclosed herein (e.g., AS treatment) can result in tumor shrinkage compared to the size of the tumor at the start of treatment. In certain embodiments, tumor shrinkage can be at least about 5% or more to at least about 10% or more, at least about 10% or more to at least about 15% or more, at least about 15% or more to at least about 20% or more, at least about 20% or more to at least about 25% or more, at least about 25% or more to at least about 30% or more, at least about 30% or more to at least about 35% or more, at least about 35% or more to at least about 40% or more, at least about 40% or more to at least about 45% or more, at least about 45% or more to at least about 50% or more, or at least about 50% or more compared to the size of the tumor at the start of treatment. or more to at least about 55% or more, at least about 55% or more to at least about 60% or more, at least about 60% or more to at least about 65% or more, at least about 65% or more to at least about 70% or more, at least about 70% or more to at least about 75% or more, at least about 75% or more to at least about 80% or more, at least about 80% or more to at least about 85% or more, at least about 85% or more to at least about 90% or more, at least about 90% or more to at least about 95% or more, at least about 95% or more to at least about 100% (i.e., complete disappearance of the tumor following treatment).

[0147] In certain embodiments, the disclosed subject may exhibit one or more cancerous solid tumors, metastatic lymph nodes, or any combination thereof. In any embodiment, a subject herein may have a cancerous tumor cell source that may be less than about 0.2 cm to at least about 20 cm or larger, at least about 2 cm to at least about 18 cm or larger, at least about 3 cm to at least about 15 cm or larger, at least about 4 cm to at least about 12 cm or larger, at least about 5 cm to at least about 10 cm or larger, or at least about 6 cm to at least about 8 cm or larger.

[0148] In certain embodiments, the disclosed methods of treating and / or preventing cancer can include a pan-tumor approach, such as, for example, administering the disclosed ANP therapies.

[0149] D. Ways to Prolong Survival Disclosed herein are methods for extending survival of a subject, the methods comprising administering a precision cancer treatment to a subject in need thereof, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment, and wherein the subject's life expectancy is extended.

[0150] Disclosed herein is a method for extending survival of a subject, the method comprising obtaining a biological sample from a subject in need thereof; subjecting the biological sample to cell-free DNA (cfDNA) analysis; diagnosing the subject as being in need of a precision cancer treatment if the expression and / or amount of one or more genomic aberrations in the biological sample is greater than the expression and / or amount of the same one or more genomic aberrations in a control sample; and administering the precision cancer treatment to the subject, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment and wherein the subject's life expectancy is extended.

[0151] Disclosed herein is a method for extending survival of a subject, the method comprising obtaining a biological sample from a subject in need thereof; subjecting the biological sample to cell-free DNA (cfDNA) analysis; diagnosing the subject as being in need of a precision cancer treatment if the expression and / or amount of one or more genomic aberrations in the biological sample is greater than the expression and / or amount of the same one or more genomic aberrations in a control sample; and administering the precision cancer treatment to the subject, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment and wherein the subject's life expectancy is extended.

[0152] Disclosed herein is a method for extending survival of a subject, the method comprising the steps of obtaining a biological sample from a subject in need thereof; subjecting the biological sample to cell-free DNA (cfDNA) analysis, wherein the expression and / or amount of one or more genomic aberrations in the biological sample is greater than the expression and / or amount of the same one or more genomic aberrations in a control sample, and diagnosing the subject as being in need of a precision cancer treatment; and administering the precision cancer treatment to the subject, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment and the subject's life expectancy is extended.

[0153] In some embodiments, the life expectancy of the subject is compared with the life expectancy of the control.In some embodiments, the control is the subject who has not received high-precision cancer treatment.In some embodiments, the control is the pooled number of subjects who have not received high-precision cancer treatment.In some embodiments, the control is one or more subjects who have the same type of cancer and the same stage as the subject.In some embodiments of the disclosed method for extending the survival of a subject, the cancer of the subject is treated.

[0154] In some embodiments, the disclosed high-precision cancer treatments may include one or more antineoplastons or may include compositions comprising one or more antineoplastons. In some embodiments, the disclosed antineoplastons may include phenylacetate, phenylacetylglutamate, sodium phenylacetylglutamate, sodium phenylacetylisoglutamate, or any combination thereof. In some embodiments, the disclosed compositions comprising one or more antineoplastons may include phenylacetate, phenylacetylglutamate, sodium phenylacetylglutamate, sodium phenylacetylisoglutamate, or any combination thereof.

[0155] In some embodiments, compositions comprising one or more disclosed antineoplastons can include a pharmaceutically acceptable carrier. In some embodiments, the one or more disclosed antineoplastons can include sodium phenylacetylglutamate (PG) and sodium phenylacetylisoglutamate (iso-PG). In some embodiments, the disclosed ratio of sodium phenylacetylglutamate (PG) to sodium phenylacetylisoglutamate (iso-PG) can be about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1, or about 1:1. In some embodiments, the disclosed ratio of sodium phenylacetylglutamate (PG) to sodium phenylacetylisoglutamate (iso-PG) can range from about 10:1 to about 1:10. In some embodiments, the disclosed ratio of sodium phenylacetylglutamate (PG) to sodium phenylacetylisoglutamate (iso-PG) can be about 4:1. In some embodiments, the disclosed dose of one or more antineoplastons can include from about 0.1 g / kg / day to about 20 g / kg / day. In some embodiments, the disclosed therapeutically effective dose of one or more disclosed antineoplastons can include from about 0.1 g / kg / day to about 20 g / kg / day. In some embodiments, the disclosed dose of sodium phenylacetylglutamate (PG) can include from about 0.4 g / kg / day to about 16 g / kg / day, and the disclosed dose of sodium phenylacetylisoglutamate (iso-PG) can include from about 0.1 g / kg / day to about 4 g / kg / day. In certain embodiments, the disclosed therapeutically effective amount of sodium phenylacetylglutamate (PG) can include from about 0.4 g / kg / day to about 16 g / kg / day, and the disclosed therapeutically effective amount of sodium phenylacetylisoglutamate (iso-PG) can include from about 0.1 g / kg / day to about 4 g / kg / day. In certain embodiments, the disclosed one or more antineoplastons can include phenylacetate (PN) and phenylacetylglutamate (PG).In some embodiments, the disclosed ratio of phenylacetate (PN) to phenylacetylglutamate (PG) can be about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1, or about 1:1. In some embodiments, the disclosed ratio of phenylacetate (PN) to phenylacetylglutamate (PG) can range from about 10:1 to about 1:10. In some embodiments, the disclosed ratio of phenylacetate (PN) to phenylacetylglutamate (PG) can be about 4:1. In some embodiments, the dose of one or more disclosed antineoplastons can include from about 0.08 g / kg / day to about 0.6 g / kg / day. In certain embodiments, a therapeutically effective dose of one or more disclosed antineoplastons can include from about 0.08 g / kg / day to about 0.6 g / kg / day. In certain embodiments, a disclosed dose of phenylacetate (PN) can include from about 0.064 g / kg / day to about 0.48 g / kg / day, and a disclosed dose of phenylacetylglutamate (PG) can include from about 0.016 g / kg / day to about 0.12 g / kg / day. In certain embodiments, a disclosed therapeutically effective dose of phenylacetate (PN) can include from about 0.064 g / kg / day to about 0.48 g / kg / day, and a disclosed therapeutically effective dose of phenylacetylglutamate (PG) can include from about 0.016 g / kg / day to about 0.12 g / kg / day.

[0156] In some embodiments of the disclosed method for prolonging the survival of a subject, the step of administering the disclosed high-precision cancer treatment can include intravenous administration. In some embodiments, the disclosed high-precision cancer treatment can be administered intravenously to a subject, for example, using a dual-channel infusion pump or two single-channel pumps and a central venous catheter. In some embodiments, the disclosed IV administration of the disclosed high-precision cancer treatment can be performed once every four hours at an infusion rate of about 50 mL per hour to about 250 mL per hour (e.g., about 50 mL per hour, about 75 mL per hour, about 100 mL per hour, about 125 mL per hour, about 150 mL per hour, about 175 mL per hour, about 200 mL per hour, about 225 mL per hour, about 250 mL per hour), depending on the subject's age and condition / tolerance.

[0157] In certain embodiments, the disclosed methods of extending survival of a subject can include titrating a dose of a disclosed high-precision cancer treatment. In certain embodiments, the disclosed methods of treating and / or preventing cancer can include titrating a dose of A10, AS2-1, or a combination thereof. In certain embodiments, the disclosed methods of treating and / or preventing cancer can include titrating a dose of a disclosed composition, a disclosed pharmaceutical composition, a disclosed therapeutic agent, a disclosed immunomodulator, a disclosed proteasome inhibitor, a disclosed small molecule, a disclosed endonuclease, a disclosed oligonucleotide, a disclosed RNA therapeutic, or any combination thereof to identify an effective dose and / or to identify an effective dose that induces only mild adverse and / or side effects.

[0158] In certain embodiments, the disclosed methods of treating and / or preventing cancer can include titrating a dose of a disclosed high-precision cancer treatment for a particular or disclosed subject. In certain embodiments, the disclosed methods of treating and / or preventing cancer can include titrating a dose of A10, AS2-1, or a combination thereof for a particular or disclosed subject. In certain embodiments, the disclosed methods of treating and / or preventing cancer can include titrating a dose of a disclosed composition, a disclosed pharmaceutical composition, a disclosed therapeutic agent, a disclosed immunomodulator, a disclosed proteasome inhibitor, a disclosed small molecule, a disclosed endonuclease, a disclosed oligonucleotide, a disclosed RNA therapeutic, or any combination thereof to identify an effective dose for a particular or disclosed subject and / or to identify an effective dose that induces only mild adverse and / or side effects.

[0159] In some embodiments, the administering step comprises administering to the subject a maximum tolerated dose of A10, AS2-1, or both. In some embodiments, the administering step comprises administering to the subject a less than maximum tolerated dose of A10, AS2-1, or both.

[0160] In some embodiments, IV administration of the disclosed high-precision cancer treatments can include outpatient settings. In some embodiments, A10 can be administered before, concurrently with, or after AS2-1 administration. In some embodiments, AS2-1 can be administered before, concurrently with, or after A10 administration. In some embodiments, the order in which one or more antineoplastons are administered can be changed during the treatment regimen.

[0161] In some embodiments, the disclosed method for prolonging the survival of a subject may further comprise obtaining a biological sample from the subject before administering the disclosed high-precision cancer treatment. In some embodiments, the disclosed method for prolonging the survival of a subject may further comprise obtaining a biological sample from the subject after administering the disclosed high-precision cancer treatment. In some embodiments, the disclosed method for prolonging the survival of a subject may further comprise subjecting the biological sample to cell-free DNA (cfDNA) analysis. cfDNA analysis is known to those skilled in the art. In some embodiments, the disclosed cfDNA analysis can be repeated one or more times. In some embodiments, the disclosed obtaining step can be repeated one or more times.

[0162] In some embodiments of the disclosed subject survival extension method, the disclosed cfDNA analysis can comprise next-generation sequencing.In some embodiments, next-generation sequencing (NGS) can comprise the use of one or more commercially available platforms.Commercially available NGS sequencing platforms can include, for example, Guardant360 CDx (Guardant Health, Inc.), FoundationOne CDx (F1CDx) (Foundation Medicine, Inc.) or Tempus xT (Tempus).

[0163] In certain embodiments of the disclosed methods of prolonging survival of a subject, the disclosed cancer-associated genes are ABL1, ABL2, ACO2, ACTB, ACVR1B, AKT, AKT1, AKT2, AKT3, ALK, AMER11, APC, AR, ARAF, ARFRP1, ARID1A, ARID1B, ARID2, ASK, ASPM, ASXL1, ATF1, ATF3, ATM, ATR, ATRX, AURKA, AURKB, AXIN1, AXL, BAD, BAGE, BAGE2, BAP1, BARD1, BAX, BCL2, BCL2L1, BCL2L2, BCL6, BCL7, BCL8, BCL9, BCL10, BCL11, BCL12, BCL13, BCL14, BCL15, BCL16, BCL17, BCL18, BCL19, BCL20, BCL210, BCL22, BCL23, BCL24, BCL25, BCL26, BCL27, BCL28, BCL29, BCL30, BCL310, BCL32, BCL33, BCL34, BCL35, BCL36, BCL37, BCL38, BCL39, BCL40, BCL410, BCL42, BCL43, BCL44, BCL45, BCL46, BCL47, BCL48, BCL49, BCL50, BCL510, BCL52, BCL53, BCL54, BCL55, BCL56, BCL57, BCL58, BCL59, BCL59, BCL59, BCL59, BCL511, BCL512, BCL513, BCL514, BCL515, BCL526, BCL53, CMA, BCOR, BCORL1, BDNF, BLM, BMPR1A, BRAF, BRCA1, BRCA2, BRD4, BRIP1, BTG1, BTK, BUB1, C10ORF54, CAGE1, CARD11, CASP5, CBFB, CBL, CCL1, CCL11, CCL1 3, CCL14, CCL15, CCL16, CCL17, CCL18, CCL19, CCL2, CCL20, CCL21, CCL22, CCL23, CCL24, CCL25, CCL26, CCL27, CCL28, CCL3, CCL4, CCL5, CCL7, CCL8, CCNA 2, CCNB 1, CCNB 2, CCND, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCR1, CCR10, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CD123, CD19, CD20, CD25, CD274, CD276 , CD30, CD33, CD4, CD79A, CD79B, CD8, CD80, CD86, CDC, CDC2, CDC20, CDC25A, CDC25B, CDC25C, CDC42, CDC6, CDC6; CDC7, CDC73, CDCA8, CDH1, CDK12 , CDK2, CDK3, CDK4, CDK6, CDK8, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, CEA, CEBPA, CFS1, CHD2, CHD4, CHEK1, CHEK2, CHK-1, CIC, CLDND1, CNE2, CREBBP, CRKL, CRLF2, CSF1, CSF1R, CSF3, CTAG1, CTAG1B, CTAG2, CTAG4, CTAG5, CTAG6, CTAG9, CTCF, CTLA4, CTNNA1, CTNNB1, CUL3, CXCL1, CXCL10,<h2 style=";text-align:left;direction:ltr">CXCL11、CXCL12、CXCL13、CXCL14、CXCL16、CXCL17、CXCL2、CXCL3、CXCL5、CX CL6、CXCL9、CXCR1、CXCR2、CXCR3、CXCR5、CXCR6、CYLD、DAXX、DCC、DDR2、DEP TOR、DICER1、DLD、DLST、DNMT3A、DOT1L、DUSP1、DUSP6、E2F1、EBNA1、EBNA2、 EGFR、EMSY、ENOX2、EP300、EPCAM、EPHA3、EPHA5、EPHA7、EPHB1、ERBB2、ERBB3 、ERBB4、ERCC1、EREG、ERG、ERK、ERRFI1、ESR1、EWSR1、EZH2、FAM46C、FANCA、 FANCC、FANCD2、FANCE、FANCF、FANCG、FANCL、FAS、FAT1、FBXW7、FGF10、FGF14 、FGF19、FGF23、FGF3、FGF4、FGF6、FGFR、FGFR1、FGFR2、FGFR3、FGFR4、FH、FL CN、FLI1、FLT1、FLT3、FLT4、FOLH1、FOLR1、FOXL2、FOXP1、FRS2、FUBP1、GABRA 6、GADD45A、GAGE1、GAGE10、GAGE12D、GAGE12F、GAGE12J、GAGE13、GAGE2A、G AGE2B、GAGE2C、GAGE2D、GAGE2E、GAGE4、GART、GATA1、GATA2、GATA3、GATA4、G ATA6、GID4、GLI1、GNA、GNA11、GNA13、GNAQ、GNAS、GPNMB、GPR124、GRIN2A、G RM3、GSK3B、H3F3A、HAVCR2、HDAC、HDAC1、HDAC5、HGF、HHLA2、HIF1、HIF1A、HI ST1H1D, HNF1A, HRAS, HSD3B1, HSP90AA1, ICOSLG, IDH1, IDH2, IDH3A, IDH3B, IDO, IGF1R, IGF2, IKBKE, IKZF1, IL1, IL15, IL1A, IL1B, IL6, IL7R, IL8, INH BA、INPP4B、IRF2、IRF4、IRS2、JAK1、JAK2、JAK3、JUN、KDM5A、KDM5C、KDM6A、 KDR、KEAP、KEL、KIT、KLHL6、KLK3、KRAS、LAG1、LAG3、LMO1、LMP1、LRP1B、LYN、LZTR1、MAD2L1、MAGEA1、MAGEA10、MAGEA12、MAGEA2、MAGEA3、MAGEA4、MAGEA5、MAGEA6、MAGEA7、MAGEA8、MAGEA9、MAGEB1、MAGEB10、MAGEB16、MAGEB18、MAGEB2、MAGEB3、MAGEB4、MAGEB6、MAGEC1、MAGEC2、MAGEC3、MAGED1、MAGED2、MAGED4、MAGED4B、MAGEE1、MAGEE2、MAGEF1、MAGEH1、MAGEL2、MAGI2、MAP2K1、MAP2K2、MAP2K4、MAP3K1、MAP3K6、MAPK、MCL1、MCM、MCM2、MCM3、MCM4、MCM5、MCM6、MCM7、MDH1、MDM2、MDM4、MED12、MEF26、MEF2B、MEN1、MET、MITF、MLH1、MLL、MLL2、MLL3、MPL、MRE11A、MSH2、MSH6、MTOR、MUC1、MUTYH、MYC、MYCL、MYCN、MYD88、MYH、MYST3、NCR3LG1、Netrin、NF1、NF2、NFE2L2、NFKB、NFKB1A、NGF、NKX2-1、NOTCH1、NOTCH2、NOTCH3、NPM1、NRAS、NSD1、NTRK1、NTRK2、NTRK3、NUP93、OGDH、ORC、ORC1、ORC1L、ORC1L;、ORC6L、ORCL、ORCLPCNA、PAK3、PALB2、PAPPA、PARK2、PAX、PAX3、PBRM1、PCNA、PDCD1、PDCD1LG2、PDGFRA、PDGFRB、PDHA1、PDK1、PGR、PIK3C2B、PIK3CA、PIK3CB、PIK3CG、PIK3R1、PIK3R2、PIK3RI、PKMYT、PKMYT1、PLCG2、PLK1、PMS2、POLD1、POLE、PPM1A、PPP2R1A、PREX2、PRKAR1A、PRKC1、PRKDC、PRSS8、PTCH1、PTEN、PTPN1、PTPN11、PTPRR、PTTG、PTTG1、PTTG2、PTTG3、QK1、RAC1、RAD50、RAD51、RAF1、RANBP1、RARA、RAS、RB1、RBL1、RBM10、RET、RICTOR、RIT1、RNF43、ROS1、RPTOR、RUNX1、RUNX1T1、SDHA、SDHB, SDHC, SDHD, SETD2, SF3B1, SKP2, SLAMF7, SLIT2, SMAD2, SMAD3, SMAD4, SMARCA4, SMARCB1, SMC1A, SMC1L1, SMO, SNCAIP, SOCS1, SOX10, SOX2, SOX9, SPAG1, SPAG11A, S PAG11B, SPAG16, SPAG17, SPAG4, SPAG5, SPAG6, SPAG7, SPAG8, SPAG9, SPEN, SPOP, SPTA1, SRC, SRSF2, STAG2, STAT3, STAT4, STAT5, STAT5B, STK11, SUCLG1, SUCLG2, SUFU, S YK, T(BRACHYURY), TAF1, TBC1D8, TBX3, TERC, TERT, TERT promoter, TET2, TFDP1, TGFRB2, TNFAIP3, TNFRSF14, TOP1, TOP2A, TOP2B, TP53, TRIB3, TSC1, TSC2, TSHR, TUBB3, TYMP, TYMS, U2AF1, UNC5A, UNC5B, VEGFA, VHL, VTCN1, WEE1, WISP3, WT1, XAGE1D, XAGE2, XAGE3, XAGE5, XCL1, XCL2, XCR1, XPO1, ZBTB2, ZNF217, ZNF703, or any combination thereof.

[0164] In certain embodiments, the disclosed cancer-associated genes can comprise one or more genomic abnormalities. In certain embodiments, a subject can have one or more genomic abnormalities in the disclosed cancer-associated genes.

[0165] In some embodiments, the disclosed ALK gene can encode an ALK protein having an I1461L or N1544K mutation. In some embodiments, the disclosed ARID2 gene can encode an ARID2 protein having an N127fs18 mutation. In some embodiments, the disclosed AKT1 gene can encode an AKT1 protein having an E17K or R346H mutation. In some embodiments, the disclosed APC gene can encode an AKT1 protein having any of the following mutations: G29G, K445K, V2716L, E918E, Q1378 * , S457 *, I1304fs, E888fs, R230C, Q1090Q, S1360P. In some embodiments, the disclosed genes may encode AR proteins having A356E, M887V, or S510R mutations. In some embodiments, the disclosed ARAF genes may encode ARAF proteins having Y495Y mutations. In some embodiments, the disclosed ARID1A genes may encode ARID1A proteins having S1798L, S1167F, G246V, R1889W, or Q802fs mutations. In some embodiments, the disclosed ARID2 genes may encode ARID2 proteins having N127fs18 mutations. In some embodiments, the disclosed ARTX genes may encode AR proteins having S850fs * 2, or s N179fs * In one embodiment, the disclosed ASXL1 gene has the R1273f mutation. * In some embodiments, the disclosed BRAF gene may encode a BRAF protein having an E264 or V600E mutation. In some embodiments, the disclosed BRCA1 gene may encode a BRAF protein having an H662Q or R1443 mutation. * In some embodiments, the disclosed BRCA2 gene may encode a BRCA2 protein having a D237N or 12040V mutation. In some embodiments, the disclosed CCND1 gene may encode a CCND1 protein having a R291W mutation. In some embodiments, the disclosed CCNE1 gene may encode a CCNE1 protein having a P268P or R95Q mutation. In some embodiments, the disclosed CDKN1B gene may encode a K59fs *In certain embodiments, the disclosed CDKN2A gene may encode a CDKN2A protein having a D74N mutation. In certain embodiments, the disclosed CTNNB1 gene may encode a CTNNB1 protein having a T41A mutation. In certain embodiments, the disclosed DDR2 gene may encode a DDR2 protein having a L749L mutation. In certain embodiments, the disclosed EGFR gene may encode an EGFR protein having a P753L, V524I, D321D, or V7421 mutation. In certain embodiments, the disclosed ERBB2 gene may encode an ERBB2 protein having a C584G or V797del (exon 20 deletion) mutation. In certain embodiments, the disclosed EWSR1 gene may encode an EWSR1 protein having an FLI1 fusion. In certain embodiments, the disclosed FBXW7 gene may encode a Y545C or R658 * In some embodiments, the disclosed FGFR genes may encode FGFR proteins having a T320T, S726F, H791H, P47P, S430fs, or R179H mutation. In some embodiments, the disclosed FGFR1 genes may encode FGFR1 proteins having a S726F mutation. In some embodiments, the disclosed FGFR2 genes may encode FGFR2 proteins having a KCNH7 fusion. In some embodiments, the disclosed FGFR3 genes may encode FGFR3 proteins having a H290Y mutation. In some embodiments, the disclosed GATA3 genes may encode GATA3 proteins having a P433fs43, P409fs, PS405fs, D336fs, S430fs, or c.1213_1214del mutation. In some embodiments, the disclosed GNA11 gene can encode a GNA11 protein having a N244S mutation. In some embodiments, the disclosed GNAS gene can encode a GNA11 protein having a R201H mutation. *In some embodiments, the disclosed HIST1H1D gene may encode a HIST1H1D protein having a K185-A186>T mutation. In some embodiments, the disclosed H3F3A gene may encode an H3F3A protein having a K28N or K27 mutation. In some embodiments, the disclosed IDH1 gene may encode an IDH1 protein having a R132H mutation. In some embodiments, the disclosed JAK2 gene may encode a JAK2 protein having a V617 mutation. In some embodiments, the disclosed KIT gene has Q775fs (exon 16 deletion). In some embodiments, the disclosed ARID1A gene may encode an ARID1A protein having a S1798L, S1167F, G246V, R1889W, or Q802fs mutation. In certain embodiments, the disclosed KRAS gene can encode a KRAS protein having a G12V, G12D, G12S, G13D, or p.AG11GD mutation. In certain embodiments, the disclosed MAP2K1 gene can encode a MAP2K1 protein having a K57E mutation. In certain embodiments, the disclosed MAP2K4 gene has a loss of exon 2. In certain embodiments, the disclosed MAP3K1 gene can encode a MAP3K1 protein having a S398 mutation. In certain embodiments, the disclosed MAP3K6 gene can encode a MAP3K6 protein having a P646L mutation. The disclosed MET gene can encode a MET protein having a C385Y, T895M, T7591, or M391 mutation. In certain embodiments, the disclosed MPL gene can encode an MPL protein having a Y591D mutation. In certain embodiments, the disclosed MYC gene can encode a MYC protein having a S244S mutation. In one embodiment, the disclosed NF1 gene comprises splice site 480-11_4801del11, splice site SNV, c.6655>T, p.D2219Y, V2378fs *In some embodiments, the disclosed NOTCH1 gene may encode a NOTCH1 protein having an A465V, V220M, D1681H, or S223N mutation, or may encode an A2617A, F710C, I1719T, or K583R mutation. In some embodiments, the disclosed NOTCH2 gene may encode a NOTCH2 protein having an S2379F mutation. In some embodiments, the disclosed NTRK1 gene may encode an NTRK1 protein having a P387L or R766Q mutation. In some embodiments, the disclosed PDGFRA gene may encode a PDGFRA protein having an E86A or V299G mutation. In some embodiments, the disclosed PIK3CA gene may encode a PIK3CA protein having a Q546H, Q546K, Q546R, Q597H, E542K, E545K, E726K, E39K, E453K, R4-P18del, H1047L, H104R, K567E, I15431, p.E545K, or G1049R mutation. In some embodiments, the disclosed PIK3R1 gene may encode a PIK3R1 protein having a S399Y408del splice site 917-1G>A mutation. In some embodiments, the disclosed PTCH1 has a p.M17 loss of start - LOF. In some embodiments, the disclosed PTEN gene has a H196_1203DEL, R55fs, N323fs mutation. * 23, Y27C, R130 * In some embodiments, the disclosed RAF1 gene can encode a PTEN protein having a Q217, C136Y, D252Y, or loss of exons 4 to 7 mutation. In some embodiments, the disclosed RAF1 gene can encode a RAF1 protein having a P63P mutation. In some embodiments, the disclosed RB1 gene can encode a PTEN protein having a Q217, C136Y, D252Y, or loss of exons 4 to 7 mutation. * , Y173fs *In certain embodiments, the disclosed RUNX1 gene may encode a RUNX1 protein having a R107C mutation. In certain embodiments, the disclosed SMAD4 gene may encode a SMAD4 protein having a P511L, D537V, Q450H, L495R, A451P, or A406T mutation. In certain embodiments, the disclosed SPEN gene may encode a SPEN protein having an A2510V mutation. In certain embodiments, the disclosed SRSF2 gene may encode an SRSF2 protein having a P95H mutation. In certain embodiments, the disclosed STAT5B gene may encode a STAT5B protein having a R110H mutation. In certain embodiments, the disclosed TET2 gene may encode a TET2 protein having a C1875G mutation. In one embodiment, the disclosed TP53 gene has the following mutations: V73fs, R175G, R196, R249T, C176F, G187D, R282W, E287 * , E285K, S241del, c.97-28_99del, Y126D, R273H, C176W, K320 * , T253A, splice site 37G-1G>A, Q104, P151H, H179Y, R273C, R248W, R176H, R209fs cer, N235-Y236del, R248Q er, R306 * , C176Y, S241F, L252-1254del, L145P, R158H, R213 * , Y220C, R110P, V274G, or c.376-4_384del mutations.

[0166] With respect to the Guardant360 platform, the disclosed genomic abnormalities in cancer-associated genes may include single nucleotide variants. For example, in certain embodiments, the disclosed single nucleotide variants may be identified in the following genes: AKT1, ALK, APC, AR, ARAF, ATM, BRAF, BRCA1, BRCA2, CCND1, CDH1, CDK4, CDK6, CDK12, CDKN2A, CTNNB1, EGFR, ERBB2, ESR1, FGFR1, FGFR2, FGFR3, GATA3, GNA11, GNAQ, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MAP2K2, MET, MLH1, MTOR, MYC, NF1, NFE2L2, NRAS, NTRK1, NTRK3, PDGFRA, PIK3CA, PTEN, RAF1, RET, RHEB, ROS1, SMAD4, SMO, STK11, TERT, TSC1, VHL, or any combination thereof. With respect to the Guardant360 platform, the disclosed genomic abnormalities of cancer-related genes can include insertions and / or deletions. For example, in some embodiments, the disclosed indels can be identified in the following genes: AKT1, ALK, APC, ATM, BRAF, BRCA1, BRCA2, CDH1, CDK12, CDKN2A, EGFR, ERBB2, ESR1, FGFR2, GATA3, HNF1A, HRAS, KIT, KRAS, MET, MLH1, NF1, PDGFRA, PIK3CA, PTEN, RET, ROS1, STK11, TSC1, VHL, or any combination thereof. With respect to the Guardant360 platform, in some embodiments, the disclosed genomic abnormalities of cancer-related genes can include copy number amplifications (CNAs). For example, in some embodiments, the disclosed CNAs can be identified in the following genes: ERBB2 and / or MET. With respect to the Guardant360 platform, in certain embodiments, the disclosed fusions may include ALK, NTRK1, RET, ROS1, or any combination thereof.

[0167] With respect to the Foundation platform, in some embodiments, the genomic abnormalities of the disclosed cancer-associated genes can include substitutions, indels, or copy number amplifications. For example, in some embodiments, the disclosed substitutions, disclosed indels, or disclosed CNAs can be identified in the following genes: ABL1, ACVR1B, AKT1, AKT2, AKT3, ALK, ALOX12B, AMER1 (FAM723B), APC, AR, ARAF, ARFRP1, ARID1A, ASXL1, ATM, ATR, ATRX, AURKA, AURKB, AXIN1, AXL, BAP1, BARD1, BCL2, BCL2L1, BCL2L2, BCL6, BCOR, BCORL1, BRAF , BRCA1, BRCA2, BRD4, BRIP1, BTG1, BTG2, BTK, C11ORF30(EMSY), CALR, CARD11, CASP8, CBFB, CBL, CCND1, CCND2, CCND3, CCNE1, CD22, CD274( PD-L7), CD70, CD79A, CD79B, CDC73, CDH1, CDK12, CDK4, CDK6, CDK8, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, CEBPA, CHEK7, CHEK2, CIC, CRE BBP, CRKL, CSFIR, CSF3R, CTCF, CTNNA1, CTNNB1, CUL3, CUL4A, CXCR4, CYP17A1, DAXX, DDR1, DDR2, DIS3, DNMT3A, DOT1L, EED, EGFR, EP300, EP HA3, EPHB1, EPHB4, ERBB2, ERBB3, ERBB4, ERCC4, ERG, ERRFI1, ESR1, EZH2, FAM46C, FANCA, FANCC, FANCG, FANCL, FAS, FBXW7, FGF10, FGF12, FG F14, FGF19, FGF23, FGF3, FGF4, FGF6, FGFR1, FGFR2, FGFR3, FGFR4, FH, FLCN, FLT1, FLT3, FOXL2, FUBP1, GABRA6, GATA3, GATA4, GATA6, GID4( C17ORF39), GNA11, GNA13, GNAQ, GNAS, GRM3, GSK3B, H3F3A, HDAC1, HGF, HNF1A, HRAS, HSD3B1, ID3, IDH1, IDH2, IGF1R, IKBKE, IKZF1, INPP4B,<h2 style=";text-align:left;direction:ltr">IRF2, IRF4, IRS2, JAK1, JAK2, JAK3, JUN, KDM5A, KDM5C, KDM6A, KDR, KEAP1, KEL, KIT, KLHL6, KMT2A(MLL), KMT2D(MLL2), KRAS, LTK, LYN, MAF, MAP2K1 (MEK1)、MAP2K2(MEK2)、MAP2K4、MAP3K1、MAP3K13、MAPK1、MCL1、MDM2、MDM 4、MED12、MEF2B、MEN1、MERTK、MET、MITF、MKNK1、MLH1、MPL、MRE11A、MSH2、M SH3、MSH6、MST1R、MTAP、MTOR、MUTYH、MYC、MYCL(MYCL1)、MYCN、MYD88、NBN 、NF1、NF2、NFE2L2、NFKBIA、NKX2-1、NOTCH1、NOTCH2、NOTCH3、NPM1、NRAS、 NT5C2、NTRK1、NTRK2、NTRK3、P2RY8、PALB2、PARK2、PARP1、PARP2、PARP3、P AX5、PBRM1、PDCD1(PD-1)、PDCD1LG2(PD-L2)、PDGFRA、PDGFRB、PDK1、PIK3C 2B、PIK3C2G、PIK3CA、PIK3CB、PIK3R1、PIM1、PMS2、POLD1、POLE、PPARG、PP 2R1A、PPP2R2A、PRDM1、PRKAR1A、PRKCI、PTCH1、PTEN、PTPN11、PTPRO、OKI、 RAC1、RAD21、RAD51、RAD51B、RAD51C、RAD51D、RAD52、RAD54L、RAF1、RARA、 RB1、RBM10、REL、RET、RICTOR、RNF43、ROS1、RPTOR、SDHA、SDHB、SDHC、SDHD、 SETD2、SF3B1、SGK1、SMAD2、SMAD4、SMARCA4、SMARCB1、SMO、SNCAIP、SOCS1 、SOX2、SOX9、SPEN、SPOP、SRC、STAG2、STAT3、STK11、SUFU、SYK、TBX3、TEK、 TET2、TGFBR2、TIPARP、TNFAIP3、TNFRSF14、TP53、TSC1、TSC2、TYRO3、U2AF 1、VEGFA、VHL、WHSC1(MMSET)、WHSC1L1、WT1、XPO1、XRCC2、ZNF217、ZNF703、Or any combination thereof. With respect to the Foundation platform, the disclosed genomic abnormalities of cancer-related genes may include rearrangements. For example, in some embodiments, the disclosed rearrangements may be identified in the following genes: ALK, BCL2, BCR, BRAF, BRCA1, BRCA2, CD74, EGFR, ETV4, ETVS, ETV6, EWSRI, EZR, FGFR1, FGFR2, FGFR3, KIT, KMT2A (MLL), MSH2, MYB, MYC, NOTCH2, NTRKI NTRK2 NUTMI, PDGFRA, RAFT, RARA, RET, ROS1, RSPO2 SDC4, SLC34A2 TERC (ncRNA), TERT (promoter only), TMPRSS2, or any combination thereof.

[0168] With respect to the Tempus platform, in some embodiments, the genomic abnormalities of the disclosed cancer-associated genes may include rearrangements. For example, in some embodiments, the disclosed rearrangements may be identified in the following genes: ABL1, ALK, BCR, BRAF, EGFR, ETV6, EWSR1, FGFR2, FGFR3, MYB, NRG1, NTRK1, NTRK2, NTRK3, PAX8, PDGFRA, PML, RARA, RET, ROS1, TFE3, TMPRSS2, or any combination thereof. With respect to the Tempus platform, in some embodiments, the genomic abnormalities of the disclosed cancer-associated genes may include single-nucleotide variants, indels, or copy number amplifications. For example, in certain embodiments, the disclosed single nucleotide variants, disclosed indels, or disclosed CNAs may be identified in the following genes: ABCB1, ABCC3, ABL1, ABL2, ABRAXAS1, ACTA2, ACVR1, (ALK2), ACVR1B, AGO1, AJUBA, AKT1, AKT2, AKT3, ALK, AMER1, APC, APLNR, APOB, AR, ARAF, ARHGAP26, ARHGAP35, ARID1A, ARID1B, ARID2, ARID5B, ASNS, ASPSCR1, ASXL1, ATIC, ATM, ATP7B, ATR, ATRX, AURKA, AURKB, AXIN1, AXIN2, AXL, B2M, BAP1, BARD1, BCL10, BCL11B, BCL2, BCL2L1, BCL2L11, BCL6, BCL7A, BCLAF1, BCOR, BCORL1, BCR, BIRC3, BLM, BMPR1A, BRAF, BRCA1, BRCA2, BRD4, BRIP1, BTG1, BTK, BUB1 B, C11orf65, C3orf70, C8orf34, CALR, CARD11, CARM1, CASP8, CASR, CBFB, CBL, CBLB, CBLC, CBR3, CCDC6, C CND1, CCND2, CCND3, CCNE1, CD19, CD22, CD274, (PD-L1), CD40, CD70, CD79A, CD79B, CDC73, CDH1, CDK12, C DK4, CDK6, CDK8, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CEBPA, CEP57, CFTR, CHD2, CHD4, CHD7,CHEK1, CHEK2, CIC, CIITA, CKS1B, CREBBP, CRKL, CRLF2, CSF1R, CSF3R, CTC1 CTCF, CTLA4, CTNNA1, CTNNB1, CTRC, CUL1, CUL3, CUL4A, CUL4B, CUX1, CXCR 4. CYLD, CYP1B1, CYP2D6, CYP3A5, CYSLTR2, DAXX, DDB2, DDR2, DDX3X, DICER 1, DIRC2, DIS3, DIS3L2, DKC1, DNM2, DNMT3A, DOT1L, DPYD, DYN, C2H1, EBF1, E CT2L, EGF, EGFR, EGLN1, EIF1AX, ELF3, ELOC, (TCEB1), EMSY, ENG, EP300, EP CAM, EPHA2, EPHA7, EPHB1, EPHB2, EPOR, ERBB2 (HER2), ERBB3, ERBB4, ERCC1 ERCC2, ERCC3, ERCC4, ERCC5, ERCC6, ERG, ERRFI1, ESR1, ETS1, ETS2, ETV1 ETV4, ETV5, ETV6, EWSR1, EZH2, FAM46C, FANCA, FANCB, FANCC, FANCD2, FANCE FANCF, FANCG, FANCI, FANCL, FANCM, FAS, FAT1, FBXO11, FBXW7, FCGR2A, FC GR3A, FDPS, FGF1, FGF10, FGF14, FGF2, FGF23, FGF3, FGF4, FGF5, FGF6, FGF7 FGF8, FGF9, FGFR1, FGFR2, FGFR3, FGFR4, FH, FHIT, FLCN, FLT1, FLT3, FLT4 FNTB, FOXA1, FOXL2, FOXO1, FOXO3, FOX, P1, FOXQ1, FRS2, FUBP1, FUSG6PD, GA BRA6、GALNT12、GATA1、GATA2、GATA3、GATA4、GATA6、GEN1、GLI1、GLI2、GNA1 1, GNA13, GNAQ, GNAS, GPC3, GPS2, GREM1, GRIN2A, GRM3, GSTP1, H19, H3F3A, H AS3, HAVCR2, HDAC1, HDAC2, HDAC4, HGF, HIF1A, HIST1H1E, HIST1H3B, HIST1 H4E、SON-A、SON-B、SON-C、SON-DMA、SON-DMB、SON-DOA、SON-DOB、SON-DPA1<h2 style=";text-align:left;direction:ltr">HLA-DPB1, HLA-DPB2, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB5, HLA-DRB6, HLA-E, HLA-F, HLA-G, HNF1A, HNF1B, HOXA1 1, HOXB13, HRAS, HSD11B2, HSD3B1, HSD3B2, HSP90AA1, HSPH1, IDH1, IDH2, IDO1, IFIT1, IFIT2, IFIT3, IFNAR1, IFNAR2, IFNGR1, IFNGR2, IFNL3, IKBKE, I KZF1, IL10RA, IL15, IL2RA, IL6R, IL7R, ING1, INPP4B, IRF1, IRF2, IRF4, IRS2, ITPKB, JAK1, JAK2, JAK3, JUN, KAT6A, KDM5A, KDM5C, KDM5D, KDM6A, KDR, K EAP1、KEL、KIF1B、KIT、KLF4、KLHL6、KLLN、KMT2A、KMT2B、KMT2C、KMT2D、KRA S、L2HGDH、LAG3、LATS1、LCK、LDLR、LEF1、LMNA、LMO1、LRP1B、LYN、LZTR1、MAD 2L2、MAF、MAFB、MAGI2、MALT1、MAP2K1、MAP2K2、MAP2K4、MAP3K1、MAP3K7、MA PK1、MAX、MC1R、MCL1、MDM2、MDM4、MED12、MEF2B、MEN1、MET、MGMT、MIB1、MITF 、MKI67、MLH1、MLH3、MLLT3、MN1、MPL、MRE11、MS4A1、MSH2、MSH3、MSH6、MTAP 、MTFD2、MTHFR、MTOR、MTRR、MUTYH、MYB、MYC、MYCL、MYCN、MYD88、MYH11、NBN 、NCOR1、NCOR2、NF1、NF2、NFE2L2、NFKBIA、NHP2、NKX2-1、NOP10、NOTCH1、NO TCH2、NOTCH3、NOTCH4、NPM1、NQO1、NRAS、NRG1、NSD1、NSD2、NT5C2、NTH、L1、N TRK1、NTRK2、NTRK3、NUDT15、NUP98、OLIG2、P2RY8、PAK1、PALB2、PALLD、PAX 3、PAX5、PAX7、PAX8、PBRM1、PCBP1、PDCD1、PDCD1LG2、PDGFRA、PDGFRB、PDK1、<h2 style=";text-align:left;direction:ltr">PHF6、PHGDH、PHLPP1、PHLPP2、PHOX2B、PIAS4、PIK3C2B、PI、K3、CA、PIK3CB、 PI、K3、CD、PIK3CG、PI、K3、R1、PIK3R2、PIM1、PLCG1、PLCG2、PML、PMS1、PMS2 、POLD1、POLE、POLH、POLQ、POT1、POU2F2、PPARA、PPARD、PPARG、PPM1D、PPP1 R15A、PPP2R1A、PPP2R2A、PPP6C、PRCC、PRDM1、PREX2、PRKAR1A、PRKDC、PRKN、 PRSS1、PTC、H、1、PTCH2、PTEN、PTPN11、PTPN13、PTPN22、PTPRD、PTPRT、QKI、 RAC1、RAD21、RAD50、RAD51、RAD51B、RAD51C、RAD51D、RAD54L、RAF1、RANBP2 、RARA、RASA1、RB1、RBM10、RECQL4、RET、RHEB、RHOA、RICTOR、RINT1、RIT1、R NF139、RNF43、ROS1、RPL5、RPS15、RPS6KB1、RPTOR、RRM1、RSF1、RUNX1、、RUNX 1T1, RXRA, SCG5, SDHA, SDHAF2, SDHB, SDHC, SDHD, SEC23B, SEMA3C, SETBP1, SETD2, SF3B1, SGK1, SH2B3, SHH, SLC26A3, SLC47A2, SLC9A3R1, SLIT2, SLX4 、SM、AD2、SMAD3、SMAD4、SMARCA1、SMARCA4、SMARCB1、SMARCE1、SMC1A、SMC3 、SMO、SOCS1、SOD2、SOX10、SOX2、SOX9、SPEN、SPINK1、SPOP、SPRED1、SRC、SRS F2, STAG2, STAT3, STAT4, STAT5A, STAT5B, STAT6, STK11, SUFU, SUZ12, SYK, SYNE1, TAF1, TANC1, TAP1, TAP2, TARBP2, TBC1D12, TBL1XR1, TBX3, TCF3, TCF 7L2、TCL1A、TERT(プロモーター)、TET2、TFE3、TFEB、TFEC、TGFBR1、TGFBR2、TIGIT 、TMEM127、TMEM173、TMPRSS2、TNF、TNFAIP3、TNFRSF14、TNFRSF17、TNFRSF9、TOP1, TOP2A, TP53, TP63, TPM1, TPMT, TRAF3, TRAF7, TSC1, TSC2, TSHR, TUSC3, TYMS, U2AF1, UBE2T, UGT1A1, UGT1A9, UMPS, VEGFA, VEGFB, VHL, VSIR, WEE1, WNK1, WNK2, WRN, WT1, XPA, XPC, XPO1, XRCC1, XRCC2, XRCC3, YEATS4, ZFHX3, ZMYM3, ZNF217, ZNF471, ZNF620, ZNF750, ZNRF3, ZRSR2, or any combination thereof.

[0169] For the Tempus platform, the following apply: APC (APC-associated conditions), ATM (Ataxia-telangiectasia, breast cancer susceptibility, pancreatic cancer susceptibility), AXIN2 (oligodontia-colorectal cancer syndrome), BAP1 (BAP1 tumor predisposition syndrome), BARD1 (breast cancer susceptibility), BLM (Bloom syndrome), BMPR1A (juvenile polyposis), BRCA1 (hereditary breast and ovarian cancer), BRCA2 (hereditary breast and ovarian cancer, Fanconi anemia), BRIP1 (ovarian cancer susceptibility, Fanconi anemia), CDH1 (hereditary gastric cancer), breast cancer susceptibility), CDK4 (melanoma susceptibility), CDKN2A (melanoma-pancreatic cancer syndrome), CEBPA (acute myeloid leukemia susceptibility), CHEK2 (breast cancer susceptibility, colon cancer susceptibility), DICER1 (DICER1 tumor predisposition syndrome), EGFR (lung cancer susceptibility, TKI resistance), EPCAM (Lynch syndrome), ETV6 (leukemia susceptibility, thrombocytopenia susceptibility), F H (hereditary leiomyomatosis and renal cell carcinoma), FLCN (Birt-Hogg-Dubé syndrome), GATA2 (GATA2 deficiency with susceptibility to myeloid malignancies), KIT (familial gastrointestinal stromal tumors), MAX (hereditary paraganglioma-pheochromocytoma syndrome), MEN1 (multiple endocrine neoplasia type 1), MET (hereditary papillary renal cell carcinoma), MLH1 (Lynch syndrome, constitutional mismatch repair deficiency), MSH2( Lynch syndrome, constitutional mismatch repair deficiency), MSH3 (MSH3-associated polyposis), MSH6 (Lynch syndrome, constitutional mismatch repair deficiency), MUTYH (MUTYH-associated polyposis), NBN (Nijmegen chromosomal instability syndrome, breast cancer susceptibility), NF1 (neurofibromatosis type 1), NF2 (neurofibromatosis type 2), NTHL1 (NTHL1 tumor syndrome, NTHL1-associated polyposis), PALB2 (breast cancer susceptibility, pancreatic cancer susceptibility, ovarian cancer susceptibility, Fanconi anemia), PDGFRA (familial gastrointestinal stromal tumor, GIST-plus syndrome), PHOX2B (neuroblastoma susceptibility), PMS2 (Lynch syndrome, constitutional mismatch repair deficiency), POLD1 (polymerase proofreading-associated polyposis), POLE (polymerase proofreading-associated polyposis), PRKAR1A (Carney complex),PTCH1 (Gorlin syndrome, basal cell nevus syndrome), PTEN (PTEN hamartoma tumor syndrome), RAD51C (ovarian cancer susceptibility, breast cancer susceptibility, Fanconi anemia), RAD51D (ovarian cancer susceptibility, breast cancer susceptibility), RB1 (retinoblastoma), RET (multiple endocrine neoplasia type 2, familial medullary thyroid carcinoma), RUNX1 (acute myeloid leukemia susceptibility), SDHA (hereditary paraganglioma-pheochromocytoma syndrome), SDHAF2 (hereditary paraganglioma-pheochromocytoma syndrome), SDHB (hereditary paraganglioma-pheochromocytoma syndrome), SDHC (hereditary paraganglioma-pheochromocytoma syndrome) , SDHD (hereditary paraganglioma-pheochromocytoma syndrome), SMAD4 (juvenile polyposis, hereditary hemorrhagic telangiectasia), SMARCA4 (rhabdoid tumor predisposition syndrome), SMARCB1 (rhabdoid tumor predisposition syndrome, schwannomatosis), STK11 (Peutz-Jeghers syndrome), SUFU (Gorlin syndrome, basal cell nevus syndrome), TMEM127 (hereditary paraganglioma-pheochromocytoma syndrome), TP53 (Li-Fraumeni syndrome), TSC1 (tuberous sclerosis complex), TSC2 (tuberous sclerosis complex), VHL (von Hippel-Lindau disease), and WT1 (WT1-associated Wilms tumor).

[0170] In some embodiments of the disclosed method for prolonging the survival of subject, next-generation sequencing can comprise the sequencing of one or more cancer-related genes.In some embodiments of the disclosed method for prolonging the survival of subject, the sequencing of one or more cancer-related genes can comprise identifying one or more genomic abnormalities.In some embodiments, one or more genomic abnormalities can comprise somatic genomic abnormalities.In some embodiments, the disclosed one or more somatic genomic abnormalities can comprise mutation, insertion, deletion, chromosome rearrangement, copy number abnormality, or any combination thereof.

[0171] In some embodiments of the disclosed method for extending the survival of a subject, the disclosed cfDNA analysis can include quantifying one or more cancer-related genes.In some embodiments, if the expression and / or amount and / or presence of one or more disclosed genomic abnormalities in biological samples before treatment is greater than the expression and / or amount and / or presence of the same one or more genomic abnormalities in control samples, the disclosed method for extending the survival of a subject can include diagnosing the subject as needing high-precision cancer treatment.In some embodiments, the disclosed control sample can be a sample obtained from a subject without cancer.In some embodiments, the disclosed control sample can be a pooled sample obtained from more than one subject without cancer.

[0172] In certain embodiments, if the expression and / or amount and / or presence of one or more disclosed genomic abnormalities in a post-treatment biological sample is less than the expression and / or amount and / or presence of the same one or more genomic abnormalities in a pre-treatment sample, the disclosed methods of prolonging a subject's survival can include continuing to administer a disclosed high-precision cancer treatment to the subject. In certain embodiments, if the expression and / or amount and / or presence of one or more disclosed genomic abnormalities in a post-treatment biological sample is less than the expression and / or amount and / or presence of the same one or more genomic abnormalities in a previous post-treatment sample, the disclosed methods of prolonging a subject's survival can include continuing to administer a disclosed high-precision cancer treatment to the subject.

[0173] In certain embodiments, the disclosed methods of extending a subject's survival may further include measuring the subject's tumor response to a high-precision cancer treatment. In certain embodiments, the subject's tumor response may include a partial response or a complete response. In certain embodiments, the disclosed partial response may include a 25% or greater reduction in tumor size or one or more tumors compared to the same tumor size or the same tumor(s) before treatment. In certain embodiments, the disclosed partial response may include a 50% or greater reduction in tumor size or one or more tumors compared to the same tumor size or the same tumor(s) before treatment. In certain embodiments, the disclosed partial response may include a 100% or greater reduction in tumor size or one or more tumors compared to the same tumor size or the same tumor(s) before treatment.

[0174] In some embodiments, the disclosed methods for prolonging the survival of a subject may further comprise measuring the subject's molecular response to the disclosed high-precision cancer treatment. In some embodiments, the disclosed molecular response may comprise a reduction in the number of somatic genomic abnormalities in the disclosed biological sample obtained from the subject. In some embodiments, the disclosed somatic genomic abnormalities may comprise mutations, insertions, deletions, chromosomal rearrangements, copy number abnormalities, fusions, or any combination thereof. In some embodiments, the disclosed methods for prolonging the survival of a subject may further comprise administering one or more additional therapeutic agents to the subject.

[0175] In certain aspects, the disclosed additional therapeutic agents can include a chemotherapeutic agent, a monoclonal antibody, a cell cycle inhibitor, a small molecule, or any combination thereof.

[0176] Monoclonal antibodies are known to those skilled in the art and may include, but are not limited to, adotrastuzumab, alemtuzumab, atezolizumab, avelumab, bevacizumab, blinatumomab, brentuximab, cemiplimab, cetuximab, daratumumab, denosumab, dinutuximab, durvalumab, elotuzumab, gemtuzumab, ibritumomab, inotuzumab, ipilimumab, necitumumab, nivolumab, obinutuzumab, ofatumumab, olaratumumab, panitumumab, pembrolizumab, pertuzumab, ramucirumab, rituximab, tositumomab, trastuzumab, or any combination thereof.

[0177] Small molecules are known to those skilled in the art. Examples of small molecules include abemaciclib, afatinib, alectinib, alpelisib, axitinib, binimetinib, bosutinib, brigatinib, cabozantinib, carfilzomib, ceritinib, gilteritinib (cgilteritinib), cobimetinib, copanlisib, crizotinib, dabrafenib, dacomitinib, dasatinib, duvelisib, encorafenib, entrectinib, erdafitinib, erlotinib, gefitinib, and ibromidine. These may include, but are not limited to, rutinib, imatinib, ivosidenib, lapatinib, larotrectinib, lenvatinib, lorlatinib, marizomib, neratinib, nilotinib, niraparib, olaparib, osimertinib, palbociclib, pazopanib, ponatinib, regorafenib, ribociclib, rucaparib, sorafenib, sunitinib, talazoparib, trametinib, vandetanib, vemurafenib, or any combination thereof. In some embodiments, the additional therapeutic agent may include bevacizumab, pazopanib, sorafenib, dasatinib, everolimus, or any combination thereof.

[0178] For example, in some embodiments, pazopanib and / or sorafenib can be orally administered to a subject at a dose of about 1 mg / kg / day to about 12 mg / kg / day, or 2 mg / kg / day to about 6 mg / kg / day. In some embodiments, the disclosed optimal dose of pazopanib and / or sorafenib can be about 3 mg / kg / day. In some embodiments, dasatinib can be orally administered to a subject at a dose of about 0.3 mg / kg / day to about 2.0 mg / kg / day, or about 0.7 mg / kg / day to about 1.4 mg / kg / day. In some embodiments, the disclosed optimal dose of dasatinib can be about 0.7 mg / kg / day. In some embodiments, everolimus can be orally administered to a subject at a dose of about 0.03 mg / kg / day to about 0.15 mg / kg / day, or about 0.03 mg / kg / day to about 0.10 mg / kg / day. In some embodiments, the disclosed optimal dose of everolimus can be about 0.07 mg / kg / day. In some embodiments, bevacizumab can be administered intravenously to a subject at a dose of about 2 mg / kg / day to about 15 mg / kg / day every 1-3 weeks, or at a dose of about 5 mg / kg / day to about 12 mg / kg / day every 1-3 weeks. In some embodiments, the disclosed optimal dose of bevacizumab can be administered intravenously to a subject at an optimal dose of about 10 mg / kg / day every 2 weeks.

[0179] In certain embodiments, the disclosed molecular markers that may determine one or more appropriate high-precision cancer treatments in one or more disclosed methods can be measured from a sample by high-density expression arrays, DNA microarrays, polymerase chain reaction (PCR), reverse transcriptase PCR (RT-PCR), real-time quantitative reverse transcription PCR (qRT-PCR), serial analysis of gene expression (SAGE), spotted cDNA arrays, GeneChips, spotted oligo arrays, bead arrays, RNA-Seq, tiling arrays, Northern blotting, hybridization microarrays, in situ hybridization, whole exome sequencing, whole genome sequencing, liquid biopsy, next-generation sequencing, or any combination thereof.

[0180] In some embodiments, the disclosed molecular markers can determine one or more appropriate high-precision cancer treatments for use in the disclosed method for prolonging the survival of a subject, and can be determined from at least one nucleic acid sequence of circulating DNA and / or RNA.In some embodiments, the disclosed molecular markers can be evaluated from circulating tumor DNA and / or RNA (ctDNA and / or ctRNA); circulating cell-free DNA and / or RNA (cfDNA, cfRNA); or any combination thereof.ctDNA / ctRNA refers to the fragmented DNA derived from tumors in the bloodstream that is not associated with cells.cfDNA / cfRNA refers to the DNA that circulates freely in the bloodstream but does not necessarily originate from tumors.In some embodiments, cfDNA / ctDNA can include any whole or fragmented genomic DNA or mitochondrial DNA, and / or cfRNA / ctRNA can include mRNA, tRNA, microRNA, small interfering RNA, and long non-coding RNA (ncRNA). In some embodiments, cfDNA and / or ctDNA can be fragmented DNA with a length of at least about 50 base pairs (bp), about 100bp, about 200bp, about 500bp, or about 1 kbp. In some embodiments, cfRNA and / or ctRNA can be full-length or fragments of mRNA (e.g., at least 70% of full length, at least 50% of full length, at least 30% of full length, etc.). In some embodiments, the disclosed molecular markers can be targeted to any cancer-related gene disclosed herein.

[0181] In certain aspects, the disclosed methods of prolonging survival of a subject can further include surgically removing one or more tumors from the subject. In certain aspects, the disclosed methods of prolonging survival of a subject can further include repeating one or more of the disclosed steps of the disclosed methods.

[0182] For example, in certain aspects, repeating one or more disclosed steps of the disclosed methods of prolonging survival of a subject can include repeating administering a precision cancer treatment to the subject, repeating measuring the subject's tumor response, repeating obtaining a biological sample from the subject, repeating subjecting the biological sample to cfDNA analysis, repeating administering one or more additional therapeutic agents, or any combination thereof.

[0183] In certain embodiments, the disclosed molecular markers can be detected, quantified, and / or analyzed over time (at various time points) to determine the effect of the disclosed precision cancer treatments (e.g., AS treatment) on a subject and / or to determine the response of the subject or the subject's tumor to the precision cancer treatment (e.g., development of resistance, susceptibility, etc.). In certain embodiments, the disclosed methods of extending subject survival can include obtaining multiple measurements from the same subject over time, and the same sample can be quantified at a single time point or over time. In certain embodiments, treatment with the disclosed treatment regimens (e.g., the disclosed precision cancer treatments comprising one or more antineoplastons) can be designed and / or determined based on the state of the cancer and / or the alteration / type of one or more molecular markers. In certain embodiments, the likelihood of success of the disclosed precision cancer treatments can be determined based on the state of the cancer and the type / quantity of one or more molecular markers.

[0184] In some embodiments, the disclosed molecular markers may be derived from genes expressed in one or more cells of a tumor or in immune cells, and may indicate an immunosuppressive tumor microenvironment, the occurrence of cancer stemness, the onset of metastasis, the state of cancer, or any combination thereof. In some embodiments, the disclosed molecular markers may be proteins or peptides encoded by the genes from which the molecular markers are derived, and can be targeted by antagonists or any other type of binding molecules to inhibit the function of the peptides.

[0185] Thus, in certain embodiments, increased expression (e.g., above a predetermined threshold) of the disclosed molecular markers derived from the disclosed genes associated with an immunosuppressive tumor microenvironment can be associated with the presence of an immunosuppressive tumor microenvironment, and can be associated with the fact that antagonists against peptides encoded by genes associated with an immunosuppressive tumor microenvironment may have a high probability of success in inhibiting the immunosuppressive tumor microenvironment and further promoting immune cell activity against tumor cells within such a microenvironment, thereby inhibiting cancer progression. In certain embodiments, once a molecular marker is identified, any appropriate antagonist against the target gene or protein product can be used. For example, in certain embodiments, a specific kinase can be targeted by a kinase inhibitor, or a specific signaling receptor can be targeted by a synthetic ligand, or a specific checkpoint receptor can be targeted by a synthetic antagonist or antibody, etc. In certain embodiments, the disclosed antagonists against the target molecules herein can be administered before, after, or in combination with AS treatment.

[0186] In some embodiments, the subject may be a human patient. In some embodiments, the subject may be of any age (e.g., elderly, adult, young adult, teenager, tween, adolescent, child, toddler, infant, or newborn), male or female, of any nationality, any ethnicity, and / or any race. In some embodiments, the subject may have terminal cancer.

[0187] In some embodiments, the disclosed subject has not received treatment prior to administration of the disclosed precision cancer treatment. In some embodiments, the disclosed subject has received treatment prior to administration of the disclosed precision cancer treatment. In some embodiments of the disclosed methods of prolonging the survival of a subject, the subject has received surgery, antibody treatment, chemotherapy treatment, radiation treatment, immunotherapy treatment, or any combination thereof prior to administration of the disclosed precision cancer treatment. In some embodiments of the disclosed methods of prolonging the survival of a subject, the subject has been diagnosed with cancer or the subject in need thereof is suspected of having cancer.

[0188] In certain embodiments, the disclosed cancers may be refractory cancers or refractory diseases. In certain embodiments, "refractory" refers to cancers and / or tumors that do not respond to treatment and / or become resistant to treatment. In certain embodiments, the subject may have relapsed disease. In certain embodiments, "relapsed" or "relapse" refers to a tumor that returns or progresses after a period of improvement with treatment (e.g., partial or complete response). In certain embodiments, the disclosed cancers may include solid tumors. In certain embodiments, the disclosed cancers may include metastatic cancers. In certain embodiments, the disclosed cancers may include terminal cancers.

[0189] In certain embodiments, the disclosed cancers include adenocarcinomas (including those of the adnexa and cervix), adenoid cystic carcinoma, adult T-cell leukemia, anaplastic astrocytoma, anaplastic ependymoma, anaplastic oligodendroglioma, astrocytoma, basal cell carcinoma, B-cell carcinoma, benign and malignant lymphoma, biliary tract-cholangiocarcinoma, intestine, brain cancers (anaplastic astrocytoma, anaplastic ependymoma, anaplastic oligodendroglioma, brainstem anaplastic astrocytoma, brainstem glioma, diffuse astrocytoma, DIPG, h3k27 mutation, ganglioglioma, glioblastoma multiforme, medulloblastoma, pilocytic astrocytoma, brainstem glioma), breast cancer, Burkitt's lymphoma, bladder cancer and bladder cancer, carcinoma of unknown primary, carcinosarcoma, cervical cancer, cholangiocarcinoma, chronic atypical myeloid leukemia, chronic atypical myeloid leukemia, colon cancer, colorectal cancer, diffuse astrocytoma, diffuse intrinsic pontine glioma (DIPG), uterine cancer, endometrial cancer, ependymoma, esophageal cancer and esophageal cancer, euthyroid Ing's sarcoma, ganglioglioma, ganglioneuroma, gastrointestinal stromal tumor (gist), glioblastoma, glioma, head and neck cancer, angiosarcoma, hepatocellular carcinoma, renal cell carcinoma, Hodgkin's disease, Kaposi's sarcoma, kidney cancer and renal carcinoma, large B-cell lymphoma, leptomeningeal carcinomatosis, leukemia, liposarcoma, liver cancer, lung cancer (non-small cell and small cell carcinoma), medulloblastoma, melanoma, meningeal sarcoma, meningioma, multiple myeloma, myelodysplastic syndrome, myeloproliferative disorders, muscle tumor, neuroblastoma, neuroendocrine carcinoma, neurofibroma, non-Hodgkin's lymphoma, oligodendroglioma, osteosarcoma, ovarian cancer and ovarian cancer, pancreatic cancer and pancreatic cancer, peripheral neuroepithelioma, peripheral T-cell lymphoma, Philadelphia chromosome positive ALL and positive CML, pilocytic astrocytoma, pineal cell tumor, pleomorphic sarcoma, pre-B cell lymphoma, primitive neuroectodermal tumor (PNET), prostate cancer and prostate cancer, refractory anemia, salivary gland cancer, sarcoma tumors, schwannoma, skin cancer and skin cancer, squamous cell carcinoma, gastric cancer and gastric cancer, synovial sarcoma, testicular cancer, thyroid cancer and thyroid cancer, T-lineage acute lymphoblastic leukemia (T-all), T-lineage lymphoblastic lymphoma (T-LL), urothelial cancer and high-grade urothelial carcinoma, uterine cancer, cervical cancer, vulvar cancer, and / or endometrial cancer, Wilms' tumor or teratocarcinoma, or any combination thereof.

[0190] In certain aspects, the disclosed cancers include breast cancer, colorectal cancer, head and neck cancer, kidney cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, brain cancer, adenoid cystic carcinoma, anaplastic astrocytoma, anaplastic ependymoma, anaplastic oligodendroglioma, brain stem glioma, diffuse astrocytoma, diffuse intrinsic pontine glioma (DIPG), ganglioglioma, medulloblastoma, pilocytic astrocytoma, cholangiocarcinoma, chronic atypical myeloid leukemia, endometrial cancer, esophageal cancer, Ewing's sarcoma, gastrointestinal stromal tumor (GIST), leptomeningeal carcinomatosis, multiple myeloma, myelodysplastic syndrome, neuroendocrine carcinoma, non-Hodgkin's lymphoma, pleomorphic sarcoma, primitive neuroectodermal tumor (PNET), refractory anemia, salivary gland cancer, skin cancer, stomach cancer, The cancers may include thyroid cancer, urothelial cancer, or any combination thereof.

[0191] In certain embodiments, the disclosed methods of extending a subject's survival may further comprise monitoring the subject for adverse effects (e.g., liver dysfunction, hematologic toxicity, neurotoxicity, skin toxicity, gastrointestinal toxicity, or any combination thereof). In certain embodiments, in the absence of adverse effects, the disclosed methods of extending a subject's survival may further comprise continuing to administer the disclosed high-precision cancer treatment to the subject. In certain embodiments, in the presence of adverse effects, the disclosed methods of extending a subject's survival may further comprise modifying one or more of the disclosed steps of the disclosed methods. In certain embodiments, the disclosed methods of extending a subject's survival may further comprise treating one or more adverse effects.

[0192] In certain aspects, the disclosed methods of prolonging survival of a subject can include modifying the disclosed administering step. In certain aspects, the disclosed modifying the administering step can include changing the amount of one or more antineoplastons or compositions comprising one or more antineoplastons administered to the subject, changing the frequency with which one or more antineoplastons or compositions comprising one or more antineoplastons are administered to the subject, changing the duration of administration of one or more antineoplastons or compositions comprising one or more antineoplastons, changing the route of administration of one or more antineoplastons or compositions comprising one or more antineoplastons administered to the subject, or any combination thereof.

[0193] In some embodiments, the disclosed method for prolonging the survival of a subject may further comprise obtaining a tissue biopsy from the subject. In some embodiments, the disclosed tissue biopsy may be subjected to next-generation sequencing. In some embodiments, the disclosed method for prolonging the survival of a subject may comprise subjecting the subject to one or more invasive or non-invasive diagnostic evaluations. Diagnostic evaluations are known in the art. In some embodiments, the disclosed non-invasive diagnostic evaluations may include X-rays, computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, ultrasound, positron emission tomography (PET) scans, or any combination thereof. In some embodiments, the disclosed invasive diagnostic evaluations may include tissue biopsies or exploratory surgery.

[0194] In some embodiments, the disclosed subject can have improved life expectancy. In some embodiments, the subject's life expectancy is compared with the life expectancy of a control. In some embodiments, the control is a subject who has not undergone high-precision cancer treatment. In some embodiments, the control is a pooled number of subjects who have not undergone high-precision cancer treatment. In some embodiments, the control is one or more subjects with the same type and stage of cancer as the subject. In some embodiments of the disclosed method for extending the survival of a subject, the subject's cancer is treated.

[0195] In certain embodiments, the disclosed methods may improve life expectancy compared to the life expectancy from cancer of an untreated subject with the same or nearly the same disease state and the same or nearly the same predicted outcome. As used herein, "life expectancy" is defined as the point at which 50 percent of subjects are alive and 50 percent are dead. In certain embodiments, a patient's life expectancy after treatment with the disclosed methods may be indefinite. In certain embodiments, a patient's life expectancy may be extended by at least about 5% or more to at least about 100%, by at least about 10% or more to at least about 95% or more, by at least about 20% or more to at least about 80% or more, or by at least about 40% or more to at least about 60% or more compared to an untreated subject with the same or nearly the same disease state and the same or nearly the same predicted outcome.

[0196] In certain embodiments, life expectancy may be increased by at least about 5% or more, at least about 10% or more, at least about 15% or more, at least about 20% or more, at least about 25% or more, at least about 30% or more, at least about 35% or more, at least about 40% or more, at least about 45% or more, at least about 50% or more, at least about 55% or more, at least about 60% or more, at least about 65% or more, at least about 70% or more, at least about 75% or more, at least about 80% or more, at least about 85% or more, at least about 90% or more, at least about 95% or more, or at least about 100% compared to an untreated subject with the same or approximately the same disease state and the same or approximately the same predicted outcome.In certain embodiments, life expectancy is at least about 5% or more to at least about 10% or more, at least about 10% or more to at least about 15% or more, at least about 15% or more to at least about 20% or more, at least about 20% or more to at least about 25% or more, at least about 25% or more to at least about 30% or more, at least about 30% or more to at least about 35% or more, at least about 35% or more to at least about 40% or more, at least about 40% or more to at least about 45% or more, at least about 45% or more to at least about 50% or more, compared to untreated patients with the same or nearly the same disease state and the same or nearly the same predicted outcome. % or more, at least about 50% or more to at least about 55% or more, at least about 55% or more to at least about 60% or more, at least about 60% or more to at least about 65% or more, at least about 65% or more to at least about 70% or more, at least about 70% or more to at least about 75% or more, at least about 75% or more to at least about 80% or more, at least about 80% or more to at least about 85% or more, at least about 85% or more to at least about 90% or more, at least about 90% or more to at least about 95% or more, at least about 95% or more to at least about 100% extended.

[0197] In some embodiments, the disclosed method for prolonging the survival of a subject can include protecting the subject from metastasis. In some embodiments, the disclosed method for prolonging the survival of a subject can include reducing the risk of developing metastasis. In some embodiments of the disclosed method for prolonging the survival of a subject, treating cancer can include increasing the subject's chance of survival, increasing the length of time before metastasis, reducing the possibility of surgical intervention, reducing the need to administer one or more additional therapeutic agents or regimens, reducing the size of one or more tumors in the subject, eliminating one or more tumors in the subject, reducing or eliminating the prevalence of one or more genomic abnormalities, restoring the normal metabolism of one or more organ systems in the subject, restoring one or more aspects of cellular homeostasis and / or cellular functionality, and / or metabolic dysregulation, or any combination thereof.

[0198] In certain embodiments of the disclosed methods of prolonging survival of a subject, restoring one or more aspects of cellular homeostasis and / or cellular functionality may include one or more of the following: (i) correcting cellular starvation in one or more cell types (e.g., liver cells and muscle cells, etc.); (ii) normalizing aspects of the autophagy pathway (e.g., correcting, preventing, reducing, and / or reversing autophagy, etc.); (iii) improving, enhancing, restoring, and / or preserving mitochondrial functionality and / or structural integrity; and (iv) organelle functionality. and / or structural integrity of cells in an organ or system affected by cancer, (v) preventing, slowing, and / or eliminating hypoglycemia, ketosis, and / or other liver abnormalities, (vi) correcting liver enzyme dysregulation, (vii) reversing, inhibiting, preventing, stabilizing, and / or slowing tumor metastasis, (viii) reversing, inhibiting, preventing, stabilizing, and / or slowing tumor growth and / or cancer spread, or (ix) any combination thereof. In certain embodiments, restoring one or more aspects of cellular homeostasis can include, for example, improving, enhancing, restoring, and / or preserving one or more aspects of the structural and / or functional integrity of cells in an organ or system affected by cancer.

[0199] For example, in certain embodiments, tumor growth may be reduced by at least about 5% or more to at least about 100%, at least about 10% or more to at least about 95% or more, at least about 20% or more to at least about 80% or more, at least about 40% or more to at least about 60% or more, compared to an untreated subject with the same or nearly the same disease state and the same or nearly the same predicted outcome. In certain embodiments, one or more tumors in a subject treated using the disclosed methods of extending subject survival may grow at least 5% (or more, as described above) less, compared to an untreated subject with the same or nearly the same disease state and the same or nearly the same predicted outcome.

[0200] In certain embodiments, tumor growth may be reduced by at least about 5% or more, at least about 10% or more, at least about 15% or more, at least about 20% or more, at least about 25% or more, at least about 30% or more, at least about 35% or more, at least about 40% or more, at least about 45% or more, at least about 50% or more, at least about 55% or more, at least about 60% or more, at least about 65% or more, at least about 70% or more, at least about 75% or more, at least about 80% or more, at least about 85% or more, at least about 90% or more, at least about 95% or more, or at least about 100% compared to an untreated subject with the same or approximately the same disease state and the same or approximately the same predicted outcome.

[0201] In certain embodiments, tumor growth is at least about 5% or more to at least about 10% or more, at least about 10% or more to at least about 15% or more, at least about 15% or more to at least about 20% or more, at least about 20% or more to at least about 25% or more, at least about 25% or more to at least about 30% or more, at least about 30% or more to at least about 35% or more, at least about 35% or more to at least about 40% or more, at least about 40% or more to at least about 45% or more, at least about 45% or more to at least about 50% or more, or It may be reduced by 0% or more, at least about 50% or more to at least about 55% or more, at least about 55% or more to at least about 60% or more, at least about 60% or more to at least about 65% or more, at least about 65% or more to at least about 70% or more, at least about 70% or more to at least about 75% or more, at least about 75% or more to at least about 80% or more, at least about 80% or more to at least about 85% or more, at least about 85% or more to at least about 90% or more, at least about 90% or more to at least about 95% or more, at least about 95% or more to at least about 100%.

[0202] In certain embodiments, treatment of a tumor according to the methods disclosed herein (e.g., AS treatment) can result in tumor shrinkage compared to the size of the tumor at the start of treatment. In certain embodiments, tumor shrinkage can be at least about 5% or more to at least about 10% or more, at least about 10% or more to at least about 15% or more, at least about 15% or more to at least about 20% or more, at least about 20% or more to at least about 25% or more, at least about 25% or more to at least about 30% or more, at least about 30% or more to at least about 35% or more, at least about 35% or more to at least about 40% or more, at least about 40% or more to at least about 45% or more, at least about 45% or more to at least about 50% or more, or at least about 50% or more compared to the size of the tumor at the start of treatment. or more to at least about 55% or more, at least about 55% or more to at least about 60% or more, at least about 60% or more to at least about 65% or more, at least about 65% or more to at least about 70% or more, at least about 70% or more to at least about 75% or more, at least about 75% or more to at least about 80% or more, at least about 80% or more to at least about 85% or more, at least about 85% or more to at least about 90% or more, at least about 90% or more to at least about 95% or more, at least about 95% or more to at least about 100% (i.e., complete disappearance of the tumor following treatment).

[0203] In certain embodiments, the disclosed subject may exhibit one or more cancerous solid tumors, metastatic nodes, or any combination thereof. In any embodiment, the subject herein may exhibit a tumor of about 0.2 cm 3 Less than ~ at least about 20cm 3 or larger, at least about 2 cm 3 ~At least about 18cm 3 or larger, at least about 3 cm 3 ~At least about 15cm 3 or larger, at least about 4 cm 3 ~At least about 12cm 3 or larger, at least about 5 cm 3 ~At least about 10cm 3 or larger, or at least about 6 cm 3 ~At least about 8cm 3 or larger.

[0204] In certain embodiments, the disclosed methods of extending survival can include a pan-tumor approach, such as, for example, administering the disclosed ANP treatments.

[0205] E. Methods of Preventing and / or Reducing Metastasis Disclosed herein are methods for preventing and / or reducing metastasis, comprising administering a precision cancer treatment to a subject in need thereof, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment, and wherein metastasis is prevented and / or reduced.

[0206] Disclosed herein is a method for preventing and / or reducing metastasis, comprising the steps of obtaining a biological sample from a subject in need thereof; subjecting the biological sample to cell-free DNA (cfDNA) analysis; diagnosing the subject as being in need of a precision cancer treatment if the expression and / or amount of one or more genomic aberrations in the biological sample is greater than the expression and / or amount of the same one or more genomic aberrations in a control sample; and administering the precision cancer treatment to the subject, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment and metastasis is prevented and / or reduced.

[0207] Disclosed herein is a method for preventing and / or reducing metastasis, comprising the steps of obtaining a biological sample from a subject in need thereof; subjecting the biological sample to cell-free DNA (cfDNA) analysis; diagnosing the subject as being in need of a precision cancer treatment if the expression and / or amount of one or more genomic aberrations in the biological sample is greater than the expression and / or amount of the same one or more genomic aberrations in a control sample; and administering the precision cancer treatment to the subject, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment and metastasis is prevented and / or reduced.

[0208] Disclosed herein is a method for preventing and / or reducing metastasis, comprising the steps of obtaining a biological sample from a subject in need thereof; subjecting the biological sample to cell-free DNA (cfDNA) analysis, wherein if the expression and / or amount of one or more genomic aberrations in the biological sample is greater than the expression and / or amount of the same one or more genomic aberrations in a control sample, diagnosing the subject as being in need of a precision cancer treatment; and administering the precision cancer treatment to the subject, wherein the subject exhibits a tumor and / or molecular response to the precision cancer treatment and metastasis is prevented and / or reduced.

[0209] In some embodiments, the life expectancy of the subject is compared with the life expectancy of a control.In some embodiments, the control is a subject that has not undergone high-precision cancer treatment.In some embodiments, the control is a pooled number of subjects that have not undergone high-precision cancer treatment.In some embodiments, the control is one or more subjects that have the same type of cancer and the same stage as the subject.In some embodiments of the disclosed method of preventing and / or reducing metastasis, the cancer of the subject is treated.

[0210] In some embodiments, the life expectancy of the subject is compared with the life expectancy of a control.In some embodiments, the control is a subject that has not undergone high-precision cancer treatment.In some embodiments, the control is a pooled number of subjects that have not undergone high-precision cancer treatment.In some embodiments, the control is one or more subjects that have the same type of cancer and the same stage as the subject.In some embodiments of the disclosed methods for preventing and / or reducing metastasis, the subject's cancer is treated.

[0211] In some embodiments, the disclosed high-precision cancer treatments may include one or more antineoplastons or may include compositions comprising one or more antineoplastons. In some embodiments, the disclosed antineoplastons may include phenylacetate, phenylacetylglutamate, sodium phenylacetylglutamate, sodium phenylacetylisoglutamate, or any combination thereof. In some embodiments, the disclosed compositions comprising one or more antineoplastons may include phenylacetate, phenylacetylglutamate, sodium phenylacetylglutamate, sodium phenylacetylisoglutamate, or any combination thereof.

[0212] In some embodiments, compositions comprising one or more disclosed antineoplastons can include a pharmaceutically acceptable carrier. In some embodiments, the one or more disclosed antineoplastons can include sodium phenylacetylglutamate (PG) and sodium phenylacetylisoglutamate (iso-PG). In some embodiments, the disclosed ratio of sodium phenylacetylglutamate (PG) to sodium phenylacetylisoglutamate (iso-PG) can be about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1, or about 1:1. In some embodiments, the disclosed ratio of sodium phenylacetylglutamate (PG) to sodium phenylacetylisoglutamate (iso-PG) can range from about 10:1 to about 1:10. In some embodiments, the disclosed ratio of sodium phenylacetylglutamate (PG) to sodium phenylacetylisoglutamate (iso-PG) can be about 4:1. In some embodiments, the disclosed dose of one or more antineoplastons can include from about 0.1 g / kg / day to about 20 g / kg / day. In some embodiments, the therapeutically effective dose of one or more disclosed antineoplastons can include from about 0.1 g / kg / day to about 20 g / kg / day. In some embodiments, the disclosed dose of sodium phenylacetylglutamate (PG) can include from about 0.4 g / kg / day to about 16 g / kg / day, and the disclosed dose of sodium phenylacetylisoglutamate (iso-PG) can include from about 0.1 g / kg / day to about 4 g / kg / day. In certain embodiments, disclosed therapeutically effective amounts of sodium phenylacetylglutamate (PG) can include from about 0.4 g / kg / day to about 16 g / kg / day, and disclosed therapeutically effective amounts of sodium phenylacetylisoglutamate (iso-PG) can include from about 0.1 g / kg / day to about 4 g / kg / day.

[0213] In some embodiments, the disclosed one or more antineoplastons can include phenylacetate (PN) and phenylacetylglutamate (PG). In some embodiments, the disclosed ratio of phenylacetate (PN) to phenylacetylglutamate (PG) can be about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1, or about 1:1. In some embodiments, the disclosed ratio of phenylacetate (PN) to phenylacetylglutamate (PG) can range from about 10:1 to about 1:10. In some embodiments, the disclosed ratio of phenylacetate (PN) to phenylacetylglutamate (PG) can be about 4:1. In some embodiments, the dose of the disclosed one or more antineoplastons can include about 0.08 g / kg / day to about 0.6 g / kg / day. In certain embodiments, a therapeutically effective dose of one or more disclosed antineoplastons can include from about 0.08 g / kg / day to about 0.6 g / kg / day. In certain embodiments, a disclosed dose of phenylacetate (PN) can include from about 0.064 g / kg / day to about 0.48 g / kg / day, and a disclosed dose of phenylacetylglutamate (PG) can include from about 0.016 g / kg / day to about 0.12 g / kg / day. In certain embodiments, a disclosed therapeutically effective dose of phenylacetate (PN) can include from about 0.064 g / kg / day to about 0.48 g / kg / day, and a disclosed therapeutically effective dose of phenylacetylglutamate (PG) can include from about 0.016 g / kg / day to about 0.12 g / kg / day.

[0214] In some embodiments of the disclosed methods for preventing and / or reducing metastasis, the step of administering the disclosed high-precision cancer treatment can include intravenous administration. In some embodiments, the disclosed high-precision cancer treatment can be administered intravenously to a subject using, for example, a dual-channel infusion pump or two single-channel pumps and a central venous catheter. In some embodiments, the disclosed IV administration of the disclosed high-precision cancer treatment can be performed once every four hours at an infusion rate of about 50 mL per hour to about 250 mL per hour (e.g., about 50 mL per hour, about 75 mL per hour, about 100 mL per hour, about 125 mL per hour, about 150 mL per hour, about 175 mL per hour, about 200 mL per hour, about 225 mL per hour, about 250 mL per hour), depending on the subject's age and condition / tolerance.

[0215] In certain embodiments, the disclosed methods of preventing and / or reducing metastasis can include titrating a dose of a disclosed high-precision cancer treatment. In certain embodiments, the disclosed methods of treating and / or preventing cancer can include titrating a dose of A10, AS2-1, or a combination thereof. In certain embodiments, the disclosed methods of treating and / or preventing cancer can include titrating a dose of a disclosed composition, a disclosed pharmaceutical composition, a disclosed therapeutic agent, a disclosed immunomodulator, a disclosed proteasome inhibitor, a disclosed small molecule, a disclosed endonuclease, a disclosed oligonucleotide, a disclosed RNA therapeutic, or any combination thereof to identify an effective dose and / or to identify an effective dose that induces only mild adverse and / or side effects.

[0216] In certain embodiments, the disclosed methods of treating and / or preventing cancer can include titrating a dose of a disclosed high-precision cancer treatment for a particular or disclosed subject. In certain embodiments, the disclosed methods of treating and / or preventing cancer can include titrating a dose of A10, AS2-1, or a combination thereof for a particular or disclosed subject. In certain embodiments, the disclosed methods of treating and / or preventing cancer can include titrating a dose of a disclosed composition, a disclosed pharmaceutical composition, a disclosed therapeutic agent, a disclosed immunomodulator, a disclosed proteasome inhibitor, a disclosed small molecule, a disclosed endonuclease, a disclosed oligonucleotide, a disclosed RNA therapeutic, or any combination thereof to identify an effective dose for a particular or disclosed subject and / or to identify an effective dose that induces only mild adverse and / or side effects.

[0217] In some embodiments, the administering step comprises administering to the subject a maximum tolerated dose of A10, AS2-1, or both. In some embodiments, the administering step comprises administering to the subject a less than maximum tolerated dose of A10, AS2-1, or both.

[0218] In some embodiments, IV administration of the disclosed high-precision cancer treatments can include outpatient settings. In some embodiments, A10 can be administered before, concurrently with, or after AS2-1 administration. In some embodiments, AS2-1 can be administered before, concurrently with, or after A10 administration. In some embodiments, the order in which one or more antineoplastons are administered can be changed during the treatment regimen.

[0219] In some embodiments, the disclosed methods for preventing and / or reducing metastasis may further comprise obtaining a biological sample from a subject before administering a disclosed high-precision cancer treatment. In some embodiments, the disclosed methods for preventing and / or reducing metastasis may further comprise obtaining a biological sample from a subject after administering a disclosed high-precision cancer treatment. In some embodiments, the disclosed methods for extending the disclosed methods for preventing and / or reducing metastasis may further comprise subjecting the biological sample to cell-free DNA (cfDNA) analysis. cfDNA analysis is known to those skilled in the art. In some embodiments, the disclosed cfDNA analysis can be repeated one or more times. In some embodiments, the disclosed obtaining step can be repeated one or more times.

[0220] In some embodiments of the disclosed method for preventing and / or reducing metastasis, the disclosed cfDNA analysis can comprise next-generation sequencing.In some embodiments, next-generation sequencing (NGS) can comprise the use of one or more commercially available platforms.Commercially available NGS sequencing platforms can include, for example, Guardant360 CDx (Guardant Health, Inc.), FoundationOne CDx (F1CDx) (Foundation Medicine, Inc.) or Tempus xT (Tempus).

[0221] In certain embodiments of the disclosed methods of preventing and / or reducing metastasis, the disclosed cancer-associated genes include ABL1, ABL2, ACO2, ACTB, ACVR1B, AKT, AKT1, AKT2, AKT3, ALK, AMER11, APC, AR, ARAF, ARFRP1, ARID1A, ARID1B, ARID2, ASK, ASPM, ASXL1, ATF1, ATF3, ATM, ATR, ATRX, AURKA, AURKB, AXIN1, AXL, BAD, BAGE, BAGE2, BAP1, BARD1, BAX, BCL2, BCL2L1, BCL2L2, BC L6, BCMA, BCOR, BCORL1, BDNF, BLM, BMPR1A, BRAF, BRCA1, BRCA2, BRD4, BRIP1, BTG1, BTK, BUB1, C10ORF54, CAGE1, CARD11, CASP5, CBFB, CBL, CCL1, CCL11, CC L13, CCL14, CCL15, CCL16, CCL17, CCL18, CCL19, CCL2, CCL20, CCL21, CCL22, CCL23, CCL24, CCL25, CCL26, CCL27, CCL28, CCL3, CCL4, CCL5, CCL7, CCL8, CCNA 2, CCNB 1, CCNB 2, CCND, CCND1, CCND2, CCND3, CCNE1, CCNE2, CCR1, CCR10, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CD123, CD19, CD20, CD25, CD274, CD2 76, CD30, CD33, CD4, CD79A, CD79B, CD8, CD80, CD86, CDC, CDC2, CDC20, CDC25A, CDC25B, CDC25C, CDC42, CDC6, CDC6; CDC7, CDC73, CDCA8, CDH1, C DK12, CDK2, CDK3, CDK4, CDK6, CDK8, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, CEA, CEBPA, CFS1, CHD2, CHD4, CHEK1, CHEK2, CHK-1, CIC, CLDND1 , CNE2, CREBBP, CRKL, CRLF2, CSF1, CSF1R, CSF3, CTAG1, CTAG1B, CTAG2, CTAG4, CTAG5, CTAG6, CTAG9, CTCF, CTLA4, CTNNA1, CTNNB1, CUL3, CXCL1,<h2 style=";text-align:left;direction:ltr">CXCL10、CXCL11、CXCL12、CXCL13、CXCL14、CXCL16、CXCL17、CXCL2、CXCL3、C XCL5, CXCL6, CXCL9, CXCR1, CXCR2, CXCR3, CXCR5, CXCR6, CYLD, DAXX, DCC, D DR2、DEPTOR、DICER1、DLD、DLST、DNMT3A、DOT1L、DUSP1、DUSP6、E2F1、EBNA1 、EBNA2、EGFR、EMSY、ENOX2、EP300、EPCAM、EPHA3、EPHA5、EPHA7、EPHB1、ERBB 2、ERBB3、ERBB4、ERCC1、EREG、ERG、ERK、ERRFI1、ESR1、EWSR1、EZH2、FAM46C 、FANCA、FANCC、FANCD2、FANCE、FANCF、FANCG、FANCL、FAS、FAT1、FBXW7、FGF 10、FGF14、FGF19、FGF23、FGF3、FGF4、FGF6、FGFR、FGFR1、FGFR2、FGFR3、FGF R4、FH、FLCN、FLI1、FLT1、FLT3、FLT4、FOLH1、FOLR1、FOXL2、FOXP1、FRS2、FUB P1、GABRA6、GADD45A、GAGE1、GAGE10、GAGE12D、GAGE12F、GAGE12J、GAGE13、 GAGE2A、GAGE2B、GAGE2C、GAGE2D、GAGE2E、GAGE4、GART、GATA1、GATA2、GATA 3、GATA4、GATA6、GID4、GLI1、GNA、GNA11、GNA13、GNAQ、GNAS、GPNMB、GPR124 、GRIN2A、GRM3、GSK3B、H3F3A、HAVCR2、HDAC、HDAC1、HDAC5、HGF、HHLA2、HIF1 HIF1A, HIST1H1D, HNF1A, HRAS, HSD3B1, HSP90AA1, ICOSLG, IDH1, IDH2, IDH3A, IDH3B, IDO, IGF1R, IGF2, IKBKE, IKZF1, IL1, IL15, IL1A, IL1B, IL6, IL 7R、IL8、INHBA、INPP4B、IRF2、IRF4、IRS2、JAK1、JAK2、JAK3、JUN、KDM5A、KD M5C、KDM6A、KDR、KEAP、KEL、KIT、KLHL6、KLK3、KRAS、LAG1、LAG3、LMO1、LMP1、LRP1B、LYN、LZTR1、MAD2L1、MAGEA1、MAGEA10、MAGEA12、MAGEA2、MAGEA3、MAGEA4、MAGEA5、MAGEA6、MAGEA7、MAGEA8、MAGEA9、MAGEB1、MAGEB10、MAGEB16、MAGEB18、MAGEB2、MAGEB3、MAGEB4、MAGEB6、MAGEC1、MAGEC2、MAGEC3、MAGED1、MAGED2、MAGED4、MAGED4B、MAGEE1、MAGEE2、MAGEF1、MAGEH1、MAGEL2、MAGI2、MAP2K1、MAP2K2、MAP2K4、MAP3K1、MAP3K6、MAPK、MCL1、MCM、MCM2、MCM3、MCM4、MCM5、MCM6、MCM7、MDH1、MDM2、MDM4、MED12、MEF26、MEF2B、MEN1、MET、MITF、MLH1、MLL、MLL2、MLL3、MPL、MRE11A、MSH2、MSH6、MTOR、MUC1、MUTYH、MYC、MYCL、MYCN、MYD88、MYH、MYST3、NCR3LG1、Netrin、NF1、NF2、NFE2L2、NFKB、NFKB1A、NGF、NKX2-1、NOTCH1、NOTCH2、NOTCH3、NPM1、NRAS、NSD1、NTRK1、NTRK2、NTRK3、NUP93、OGDH、ORC、ORC1、ORC1L、ORC1L;、ORC6L、ORCL、ORCLPCNA、PAK3、PALB2、PAPPA、PARK2、PAX、PAX3、PBRM1、PCNA、PDCD1、PDCD1LG2、PDGFRA、PDGFRB、PDHA1、PDK1、PGR、PIK3C2B、PIK3CA、PIK3CB、PIK3CG、PIK3R1、PIK3R2、PIK3RI、PKMYT、PKMYT1、PLCG2、PLK1、PMS2、POLD1、POLE、PPM1A、PPP2R1A、PREX2、PRKAR1A、PRKC1、PRKDC、PRSS8、PTCH1、PTEN、PTPN1、PTPN11、PTPRR、PTTG、PTTG1、PTTG2、PTTG3、QK1、RAC1、RAD50、RAD51、RAF1、RANBP1、RARA、RAS、RB1、RBL1、RBM10、RET、RICTOR、RIT1、RNF43、ROS1、RPTOR、RUNX1、RUNX1T1, SDHA, SDHB, SDHC, SDHD, SETD2, SF3B1, SKP2, SLAMF7, SLIT2, SMAD2, SMAD3, SMAD4, SMARCA4, SMARCB1, SMC1A, SMC1L1, SMO, SNCAIP, SOCS1, SOX10, SOX2, SOX9, SPAG1 , SPAG11A, SPAG11B, SPAG16, SPAG17, SPAG4, SPAG5, SPAG6, SPAG7, SPAG8, SPAG9, SPEN, SPOP, SPTA1, SRC, SRSF2, STAG2, STAT3, STAT4, STAT5, STAT5B, STK11, SUCLG1, SUCLG2, SUFU, SYK, T(BRACHYURY), TAF1, TBC1D8, TBX3, TERC, TERT, TERT promoter, TET2, TFDP1, TGFRB2, TNFAIP3, TNFRSF14, TOP1, TOP2A, TOP2B, TP53, TRIB3, TSC1, TSC2, TSHR, TUBB3, TYMP, TYMS, U2AF1, UNC5A, UNC5B, VEGFA, VHL, VTCN1, WEE1, WISP3, WT1, XAGE1D, XAGE2, XAGE3, XAGE5, XCL1, XCL2, XCR1, XPO1, ZBTB2, ZNF217, ZNF703, or any combination thereof.

[0222] In certain embodiments, the disclosed cancer-associated genes can comprise one or more genomic abnormalities. In certain embodiments, a subject can have one or more genomic abnormalities in the disclosed cancer-associated genes.

[0223] In some embodiments, the disclosed ALK gene can encode an ALK protein having an I1461L or N1544K mutation. In some embodiments, the disclosed ARID2 gene can encode an ARID2 protein having an N127fs18 mutation. In some embodiments, the disclosed AKT1 gene can encode an AKT1 protein having an E17K or R346H mutation. In some embodiments, the disclosed APC gene can encode an APC protein having G29G, K445K, V2716L, E918E, Q1378*, S457*, I1304fs, E888fs, R230C, Q1090Q, S1360P. In some embodiments, the disclosed gene can encode an AR protein having an A356E, M887V, or S510R mutation. In some embodiments, the disclosed ARAF gene can encode an ARAF protein having a Y495Y mutation. In some embodiments, the disclosed ARID1A gene may encode an ARID1A protein having a S1798L, S1167F, G246V, R1889W, or Q802fs mutation. In some embodiments, the disclosed ARID2 gene may encode an ARID2 protein having a N127fs18 mutation. In some embodiments, the disclosed ARTX gene has a S850fs*2 or N179fs*26 mutation. In some embodiments, the disclosed ASXL1 gene has a R1273f*s mutation. In some embodiments, the disclosed BRAF gene may encode a BRAF protein having an E264 or V600E mutation. In some embodiments, the disclosed BRCA1 gene may encode a BRAC1 protein having a H662Q or R1443* mutation. In some embodiments, the disclosed BRCA2 gene may encode a BRCA2 protein having a D237N or 12040V mutation. In certain embodiments, the disclosed CCND1 gene can encode a CCND1 protein having a R291W mutation. In certain embodiments, the disclosed CCNE1 gene can encode a CCNE1 protein having a P268P or R95Q mutation. In certain embodiments, the disclosed CDKN1B gene can encode a CDKN1B protein having a K59fs* mutation. In certain embodiments, the disclosed CDKN2A gene can encode a CDKN2A protein having a D74N mutation.In some embodiments, the disclosed CTNNB1 gene can encode a CTNNB1 protein having a T41A mutation. In some embodiments, the disclosed DDR2 gene can encode a DDR2 protein having a L749L mutation. In some embodiments, the disclosed EGFR gene can encode an EGFR protein having a P753L, V524I, D321D, or V7421 mutation. In some embodiments, the disclosed ERBB2 gene can encode an ERBB2 protein having a C584G or V797del (exon 20 deletion) mutation. In some embodiments, the disclosed EWSR1 gene can encode an EWSR1 protein having an FLI1 fusion. In some embodiments, the disclosed FBXW7 gene can encode an FBXW7 protein having a Y545C or R658* mutation. In some embodiments, the disclosed FGFR genes may encode FGFR proteins having a T320T, S726F, H791H, P47P, S430fs, or R179H mutation. In some embodiments, the disclosed FGFR1 genes may encode FGFR1 proteins having a S726F mutation. In some embodiments, the disclosed FGFR2 genes may encode FGFR2 proteins having a KCNH7 fusion. In some embodiments, the disclosed FGFR3 genes may encode FGFR3 proteins having a H290Y mutation. In some embodiments, the disclosed GATA3 genes may encode GATA3 proteins having a P433fs43, P409fs, PS405fs, D336fs, S430fs, or c.1213_1214del mutation. In some embodiments, the disclosed GNA11 genes may encode GNA11 proteins having a N244S mutation. In some embodiments, the disclosed GNAS gene can encode a GNAS protein having a R201H* mutation. In some embodiments, the disclosed HIST1H1D gene can encode a HIST1H1D protein having a K185-A186>T mutation. In some embodiments, the disclosed H3F3A gene can encode an H3F3A protein having a K28N or K27 mutation. In some embodiments, the disclosed IDH1 gene can encode an IDH1 protein having a R132H mutation.In some embodiments, the disclosed JAK2 gene can encode a JAK2 protein having a V617 mutation. In some embodiments, the disclosed KIT gene has a Q775fs (deletion of exon 16). In some embodiments, the disclosed ARID1A gene can encode an ARID1A protein having a S1798L, S1167F, G246V, R1889W, or Q802fs mutation. In some embodiments, the disclosed KRAS gene can encode a KRAS protein having a G12V, G12D, G12S, G13D, or p.AG11GD mutation. In some embodiments, the disclosed MAP2K1 gene can encode a MAP2K1 protein having a K57E mutation. In some embodiments, the disclosed MAP2K4 gene has a loss of exon 2. In some embodiments, the disclosed MAP3K1 gene can encode a MAP3K1 protein having a S398 mutation. In some embodiments, the disclosed MAP3K6 gene can encode a MAP3K6 protein having a P646L mutation. The disclosed MET gene can encode a MET protein having a C385Y, T895M, T7591, or M391 mutation. In some embodiments, the disclosed MPL gene can encode an MPL protein having a Y591D mutation. In some embodiments, the disclosed MYC gene can encode a MYC protein having a S244S mutation. In some embodiments, the disclosed NF1 gene can have splice site 480-11_4801del11, splice site SNV, c.6655>T, p.D2219Y, V2378fs*8, or encode an A2617A, F710C, I1719T, or K583R mutation. In some embodiments, the disclosed NOTCH1 gene can encode a NOTCH1 protein having an A465V, V220M, D1681H, or S223N mutation. In some embodiments, the disclosed NOTCH2 gene can encode a NOTCH2 protein having an S2379F mutation. In some embodiments, the disclosed NTRK1 gene can encode an NTRK1 protein having a P387L or R766Q mutation. In some embodiments, the disclosed PDGFRA gene can encode a PDGFRA protein having an E86A or V299G mutation.In some embodiments, the disclosed PIK3CA gene can encode a PIK3CA protein having a Q546H, Q546K, Q546R, Q597H, E542K, E545K, E726K, E39K, E453K, R4-P18del, H1047L, H104R, K567E, I15431, p.E545K, or G1049R mutation. In some embodiments, the disclosed PIK3R1 gene can encode a PIK3R1 protein having a S399Y408del splice site 917-1G>A mutation. In some embodiments, the disclosed PTCH1 has a p.M17 loss of start - LOF. In certain embodiments, the disclosed PTEN gene can encode a PTEN protein having an H196_1203DEL, R55fs, N323fs*23, Y27C, R130*, C136Y, D252Y, or a loss mutation in exons 4-7. In certain embodiments, the disclosed RAF1 gene can encode a RAF1 protein having a P63P mutation. In certain embodiments, the disclosed RB1 gene can encode a RB1 protein having a Q217*, Y173fs*, or H673fs mutation. In certain embodiments, the disclosed RUNX1 gene can encode a RUNX1 protein having an R107C mutation. In certain embodiments, the disclosed SMAD4 gene can encode a SMAD4 protein having a P511L, D537V, Q450H, L495R, A451P, or A406T mutation. In some embodiments, the disclosed SPEN gene can encode a SPEN protein having an A2510V mutation. In some embodiments, the disclosed SRSF2 gene can encode a SRSF2 protein having a P95H mutation. In some embodiments, the disclosed STAT5B gene can encode a STAT5B protein having an R110H mutation. In some embodiments, the disclosed TET2 gene can encode a TET2 protein having a C1875G mutation.In one embodiment, the disclosed TP53 gene is V73fs, R175G, R196, R249T, C176F, G187D, R282W, E287*, E285K, S241del, c.97-28_99del, Y126D, R273H, C176W, K320*, T253A, splice site 37G-1G>A, Q104, P151H, H179Y, R273C, R248W, R176H, R209fs cer, N235-Y236del, R248Q er, R306*, C176Y, S241F, L252-1254del, L145P, R158H, R213*, Y220C, R110P, V274G, or c.376-4_384del mutations.

[0224] With respect to the Guardant360 platform, the disclosed genomic abnormalities in cancer-associated genes may include single nucleotide variants. For example, in certain embodiments, the disclosed single nucleotide variants may be identified in the following genes: AKT1, ALK, APC, AR, ARAF, ATM, BRAF, BRCA1, BRCA2, CCND1, CDH1, CDK4, CDK6, CDK12, CDKN2A, CTNNB1, EGFR, ERBB2, ESR1, FGFR1, FGFR2, FGFR3, GATA3, GNA11, GNAQ, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MAP2K2, MET, MLH1, MTOR, MYC, NF1, NFE2L2, NRAS, NTRK1, NTRK3, PDGFRA, PIK3CA, PTEN, RAF1, RET, RHEB, ROS1, SMAD4, SMO, STK11, TERT, TSC1, VHL, or any combination thereof. With respect to the Guardant360 platform, the disclosed genomic abnormalities of cancer-related genes can include insertions and / or deletions. For example, in some embodiments, the disclosed indels can be identified in the following genes: AKT1, ALK, APC, ATM, BRAF, BRCA1, BRCA2, CDH1, CDK12, CDKN2A, EGFR, ERBB2, ESR1, FGFR2, GATA3, HNF1A, HRAS, KIT, KRAS, MET, MLH1, NF1, PDGFRA, PIK3CA, PTEN, RET, ROS1, STK11, TSC1, VHL, or any combination thereof. With respect to the Guardant360 platform, in some embodiments, the disclosed genomic abnormalities of cancer-related genes can include copy number amplifications (CNAs). For example, in some embodiments, the disclosed CNAs can be identified in the following genes: ERBB2 and / or MET. With respect to the Guardant360 platform, in certain embodiments, the disclosed fusions may include ALK, NTRK1, RET, ROS1, or any combination thereof.

[0225] With respect to the Foundation platform, in some embodiments, the genomic abnormalities of the disclosed cancer-associated genes can include substitutions, indels, or copy number amplifications. For example, in some embodiments, the disclosed substitutions, disclosed indels, or disclosed CNAs can be identified in the following genes: ABL1, ACVR1B, AKT1, AKT2, AKT3, ALK, ALOX12B, AMER1 (FAM723B), APC, AR, ARAF, ARFRP1, ARID1A, ASXL1, ATM, ATR, ATRX, AURKA, AURKB, AXIN1, AXL, BAP1, BARD1, BCL2, BCL2L1, BCL2L2, BCL6, BCOR, BCORL1, BRAF , BRCA1, BRCA2, BRD4, BRIP1, BTG1, BTG2, BTK, C11ORF30(EMSY), CALR, CARD11, CASP8, CBFB, CBL, CCND1, CCND2, CCND3, CCNE1, CD22, CD274( PD-L7), CD70, CD79A, CD79B, CDC73, CDH1, CDK12, CDK4, CDK6, CDK8, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, CEBPA, CHEK7, CHEK2, CIC, CRE BBP, CRKL, CSFIR, CSF3R, CTCF, CTNNA1, CTNNB1, CUL3, CUL4A, CXCR4, CYP17A1, DAXX, DDR1, DDR2, DIS3, DNMT3A, DOT1L, EED, EGFR, EP300, EP HA3, EPHB1, EPHB4, ERBB2, ERBB3, ERBB4, ERCC4, ERG, ERRFI1, ESR1, EZH2, FAM46C, FANCA, FANCC, FANCG, FANCL, FAS, FBXW7, FGF10, FGF12, FG F14, FGF19, FGF23, FGF3, FGF4, FGF6, FGFR1, FGFR2, FGFR3, FGFR4, FH, FLCN, FLT1, FLT3, FOXL2, FUBP1, GABRA6, GATA3, GATA4, GATA6, GID4( C17ORF39), GNA11, GNA13, GNAQ, GNAS, GRM3, GSK3B, H3F3A, HDAC1, HGF, HNF1A, HRAS, HSD3B1, ID3, IDH1, IDH2, IGF1R, IKBKE, IKZF1, INPP4B,<h2 style=";text-align:left;direction:ltr">IRF2, IRF4, IRS2, JAK1, JAK2, JAK3, JUN, KDM5A, KDM5C, KDM6A, KDR, KEAP1, KEL, KIT, KLHL6, KMT2A(MLL), KMT2D(MLL2), KRAS, LTK, LYN, MAF, MAP2K1 (MEK1)、MAP2K2(MEK2)、MAP2K4、MAP3K1、MAP3K13、MAPK1、MCL1、MDM2、MDM 4、MED12、MEF2B、MEN1、MERTK、MET、MITF、MKNK1、MLH1、MPL、MRE11A、MSH2、M SH3、MSH6、MST1R、MTAP、MTOR、MUTYH、MYC、MYCL(MYCL1)、MYCN、MYD88、NBN 、NF1、NF2、NFE2L2、NFKBIA、NKX2-1、NOTCH1、NOTCH2、NOTCH3、NPM1、NRAS、 NT5C2、NTRK1、NTRK2、NTRK3、P2RY8、PALB2、PARK2、PARP1、PARP2、PARP3、P AX5、PBRM1、PDCD1(PD-1)、PDCD1LG2(PD-L2)、PDGFRA、PDGFRB、PDK1、PIK3C 2B、PIK3C2G、PIK3CA、PIK3CB、PIK3R1、PIM1、PMS2、POLD1、POLE、PPARG、PP 2R1A、PPP2R2A、PRDM1、PRKAR1A、PRKCI、PTCH1、PTEN、PTPN11、PTPRO、OKI、 RAC1、RAD21、RAD51、RAD51B、RAD51C、RAD51D、RAD52、RAD54L、RAF1、RARA、 RB1、RBM10、REL、RET、RICTOR、RNF43、ROS1、RPTOR、SDHA、SDHB、SDHC、SDHD、 SETD2、SF3B1、SGK1、SMAD2、SMAD4、SMARCA4、SMARCB1、SMO、SNCAIP、SOCS1 、SOX2、SOX9、SPEN、SPOP、SRC、STAG2、STAT3、STK11、SUFU、SYK、TBX3、TEK、 TET2、TGFBR2、TIPARP、TNFAIP3、TNFRSF14、TP53、TSC1、TSC2、TYRO3、U2AF 1、VEGFA、VHL、WHSC1(MMSET)、WHSC1L1、WT1、XPO1、XRCC2、ZNF217、ZNF703、Or any combination thereof. With respect to the Foundation platform, the disclosed genomic abnormalities of cancer-related genes may include rearrangements. For example, in some embodiments, the disclosed rearrangements may be identified in the following genes: ALK, BCL2, BCR, BRAF, BRCA1, BRCA2, CD74, EGFR, ETV4, ETVS, ETV6, EWSRI, EZR, FGFR1, FGFR2, FGFR3, KIT, KMT2A (MLL), MSH2, MYB, MYC, NOTCH2, NTRKI NTRK2 NUTMI, PDGFRA, RAFT, RARA, RET, ROS1, RSPO2 SDC4, SLC34A2 TERC (ncRNA), TERT (promoter only), TMPRSS2, or any combination thereof.

[0226] With respect to the Tempus platform, in some embodiments, the genomic abnormalities of the disclosed cancer-associated genes may include rearrangements. For example, in some embodiments, the disclosed rearrangements may be identified in the following genes: ABL1, ALK, BCR, BRAF, EGFR, ETV6, EWSR1, FGFR2, FGFR3, MYB, NRG1, NTRK1, NTRK2, NTRK3, PAX8, PDGFRA, PML, RARA, RET, ROS1, TFE3, TMPRSS2, or any combination thereof. With respect to the Tempus platform, in some embodiments, the genomic abnormalities of the disclosed cancer-associated genes may include single-nucleotide variants, indels, or copy number amplifications. For example, in certain embodiments, the disclosed single nucleotide variants, disclosed indels, or disclosed CNAs may be identified in the following genes: ABCB1, ABCC3, ABL1, ABL2, ABRAXAS1, ACTA2, ACVR1, (ALK2), ACVR1B, AGO1, AJUBA, AKT1, AKT2, AKT3, ALK, AMER1, APC, APLNR, APOB, AR, ARAF, ARHGAP26, ARHGAP35, ARID1A, ARID1B, ARID2, ARID5B, ASNS, ASPSCR1, ASXL1, ATIC, ATM, ATP7B, ATR, ATRX, AURKA, AURKB, AXIN1, AXIN2, AXL, B2M, BAP1, BARD1, BCL10, BCL11B, BCL2, BCL2L1, BCL2L11, BCL6, BCL7A, BCLAF1, BCOR, BCORL1, BCR, BIRC3, BLM, BMPR1A, BRAF, BRCA1, BRCA2, BRD4, BRIP1, BTG1, BTK, BUB1 B, C11orf65, C3orf70, C8orf34, CALR, CARD11, CARM1, CASP8, CASR, CBFB, CBL, CBLB, CBLC, CBR3, CCDC6, C CND1, CCND2, CCND3, CCNE1, CD19, CD22, CD274, (PD-L1), CD40, CD70, CD79A, CD79B, CDC73, CDH1, CDK12, C DK4, CDK6, CDK8, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2B, CDKN2C, CEBPA, CEP57, CFTR, CHD2, CHD4, CHD7,CHEK1, CHEK2, CIC, CIITA, CKS1B, CREBBP, CRKL, CRLF2, CSF1R, CSF3R, CTC1 CTCF, CTLA4, CTNNA1, CTNNB1, CTRC, CUL1, CUL3, CUL4A, CUL4B, CUX1, CXCR 4. CYLD, CYP1B1, CYP2D6, CYP3A5, CYSLTR2, DAXX, DDB2, DDR2, DDX3X, DICER 1, DIRC2, DIS3, DIS3L2, DKC1, DNM2, DNMT3A, DOT1L, DPYD, DYN, C2H1, EBF1, E CT2L, EGF, EGFR, EGLN1, EIF1AX, ELF3, ELOC, (TCEB1), EMSY, ENG, EP300, EP CAM, EPHA2, EPHA7, EPHB1, EPHB2, EPOR, ERBB2 (HER2), ERBB3, ERBB4, ERCC1 ERCC2, ERCC3, ERCC4, ERCC5, ERCC6, ERG, ERRFI1, ESR1, ETS1, ETS2, ETV1 ETV4, ETV5, ETV6, EWSR1, EZH2, FAM46C, FANCA, FANCB, FANCC, FANCD2, FANCE FANCF, FANCG, FANCI, FANCL, FANCM, FAS, FAT1, FBXO11, FBXW7, FCGR2A, FC GR3A, FDPS, FGF1, FGF10, FGF14, FGF2, FGF23, FGF3, FGF4, FGF5, FGF6, FGF7 FGF8, FGF9, FGFR1, FGFR2, FGFR3, FGFR4, FH, FHIT, FLCN, FLT1, FLT3, FLT4 FNTB, FOXA1, FOXL2, FOXO1, FOXO3, FOX, P1, FOXQ1, FRS2, FUBP1, FUSG6PD, GA BRA6、GALNT12、GATA1、GATA2、GATA3、GATA4、GATA6、GEN1、GLI1、GLI2、GNA1 1, GNA13, GNAQ, GNAS, GPC3, GPS2, GREM1, GRIN2A, GRM3, GSTP1, H19, H3F3A, H AS3, HAVCR2, HDAC1, HDAC2, HDAC4, HGF, HIF1A, HIST1H1E, HIST1H3B, HIST1 H4E、SON-A、SON-B、SON-C、SON-DMA、SON-DMB、SON-DOA、SON-DOB、SON-DPA1<h2 style=";text-align:left;direction:ltr">HLA-DPB1, HLA-DPB2, HLA-DQA1, HLA-DQA2, HLA-DQB1, HLA-DQB2, HLA-DRA, HLA-DRB1, HLA-DRB5, HLA-DRB6, HLA-E, HLA-F, HLA-G, HNF1A, HNF1B, HOXA1 1, HOXB13, HRAS, HSD11B2, HSD3B1, HSD3B2, HSP90AA1, HSPH1, IDH1, IDH2, IDO1, IFIT1, IFIT2, IFIT3, IFNAR1, IFNAR2, IFNGR1, IFNGR2, IFNL3, IKBKE, I KZF1, IL10RA, IL15, IL2RA, IL6R, IL7R, ING1, INPP4B, IRF1, IRF2, IRF4, IRS2, ITPKB, JAK1, JAK2, JAK3, JUN, KAT6A, KDM5A, KDM5C, KDM5D, KDM6A, KDR, K EAP1、KEL、KIF1B、KIT、KLF4、KLHL6、KLLN、KMT2A、KMT2B、KMT2C、KMT2D、KRA S、L2HGDH、LAG3、LATS1、LCK、LDLR、LEF1、LMNA、LMO1、LRP1B、LYN、LZTR1、MAD 2L2、MAF、MAFB、MAGI2、MALT1、MAP2K1、MAP2K2、MAP2K4、MAP3K1、MAP3K7、MA PK1、MAX、MC1R、MCL1、MDM2、MDM4、MED12、MEF2B、MEN1、MET、MGMT、MIB1、MITF 、MKI67、MLH1、MLH3、MLLT3、MN1、MPL、MRE11、MS4A1、MSH2、MSH3、MSH6、MTAP 、MTFD2、MTHFR、MTOR、MTRR、MUTYH、MYB、MYC、MYCL、MYCN、MYD88、MYH11、NBN 、NCOR1、NCOR2、NF1、NF2、NFE2L2、NFKBIA、NHP2、NKX2-1、NOP10、NOTCH1、NO TCH2、NOTCH3、NOTCH4、NPM1、NQO1、NRAS、NRG1、NSD1、NSD2、NT5C2、NTH、L1、N TRK1、NTRK2、NTRK3、NUDT15、NUP98、OLIG2、P2RY8、PAK1、PALB2、PALLD、PAX 3、PAX5、PAX7、PAX8、PBRM1、PCBP1、PDCD1、PDCD1LG2、PDGFRA、PDGFRB、PDK1、<h2 style=";text-align:left;direction:ltr">PHF6、PHGDH、PHLPP1、PHLPP2、PHOX2B、PIAS4、PIK3C2B、PI、K3、CA、PIK3CB、 PI、K3、CD、PIK3CG、PI、K3、R1、PIK3R2、PIM1、PLCG1、PLCG2、PML、PMS1、PMS2 、POLD1、POLE、POLH、POLQ、POT1、POU2F2、PPARA、PPARD、PPARG、PPM1D、PPP1 R15A、PPP2R1A、PPP2R2A、PPP6C、PRCC、PRDM1、PREX2、PRKAR1A、PRKDC、PRKN、 PRSS1、PTC、H、1、PTCH2、PTEN、PTPN11、PTPN13、PTPN22、PTPRD、PTPRT、QKI、 RAC1、RAD21、RAD50、RAD51、RAD51B、RAD51C、RAD51D、RAD54L、RAF1、RANBP2 、RARA、RASA1、RB1、RBM10、RECQL4、RET、RHEB、RHOA、RICTOR、RINT1、RIT1、R NF139、RNF43、ROS1、RPL5、RPS15、RPS6KB1、RPTOR、RRM1、RSF1、RUNX1、、RUNX 1T1, RXRA, SCG5, SDHA, SDHAF2, SDHB, SDHC, SDHD, SEC23B, SEMA3C, SETBP1, SETD2, SF3B1, SGK1, SH2B3, SHH, SLC26A3, SLC47A2, SLC9A3R1, SLIT2, SLX4 、SM、AD2、SMAD3、SMAD4、SMARCA1、SMARCA4、SMARCB1、SMARCE1、SMC1A、SMC3 、SMO、SOCS1、SOD2、SOX10、SOX2、SOX9、SPEN、SPINK1、SPOP、SPRED1、SRC、SRS F2, STAG2, STAT3, STAT4, STAT5A, STAT5B, STAT6, STK11, SUFU, SUZ12, SYK, SYNE1, TAF1, TANC1, TAP1, TAP2, TARBP2, TBC1D12, TBL1XR1, TBX3, TCF3, TCF 7L2、TCL1A、TERT(プロモーター)、TET2、TFE3、TFEB、TFEC、TGFBR1、TGFBR2、TIGIT 、TMEM127、TMEM173、TMPRSS2、TNF、TNFAIP3、TNFRSF14、TNFRSF17、TNFRSF9、TOP1, TOP2A, TP53, TP63, TPM1, TPMT, TRAF3, TRAF7, TSC1, TSC2, TSHR, TUSC3, TYMS, U2AF1, UBE2T, UGT1A1, UGT1A9, UMPS, VEGFA, VEGFB, VHL, VSIR, WEE1, WNK1, WNK2, WRN, WT1, XPA, XPC, XPO1, XRCC1, XRCC2, XRCC3, YEATS4, ZFHX3, ZMYM3, ZNF217, ZNF471, ZNF620, ZNF750, ZNRF3, ZRSR2, or any combination thereof.

[0227] For the Tempus platform, the following apply: APC (APC-associated conditions), ATM (Ataxia-telangiectasia, breast cancer susceptibility, pancreatic cancer susceptibility), AXIN2 (oligodontia-colorectal cancer syndrome), BAP1 (BAP1 tumor predisposition syndrome), BARD1 (breast cancer susceptibility), BLM (Bloom syndrome), BMPR1A (juvenile polyposis), BRCA1 (hereditary breast and ovarian cancer), BRCA2 (hereditary breast and ovarian cancer, Fanconi anemia), BRIP1 (ovarian cancer susceptibility, Fanconi anemia), CDH1 (hereditary gastric cancer), breast cancer susceptibility), CDK4 (melanoma susceptibility), CDKN2A (melanoma-pancreatic cancer syndrome), CEBPA (acute myeloid leukemia susceptibility), CHEK2 (breast cancer susceptibility, colon cancer susceptibility), DICER1 (DICER1 tumor predisposition syndrome), EGFR (lung cancer susceptibility, TKI resistance), EPCAM (Lynch syndrome), ETV6 (leukemia susceptibility, thrombocytopenia susceptibility), F H (hereditary leiomyomatosis and renal cell carcinoma), FLCN (Birt-Hogg-Dubé syndrome), GATA2 (GATA2 deficiency with susceptibility to myeloid malignancies), KIT (familial gastrointestinal stromal tumors), MAX (hereditary paraganglioma-pheochromocytoma syndrome), MEN1 (multiple endocrine neoplasia type 1), MET (hereditary papillary renal cell carcinoma), MLH1 (Lynch syndrome, constitutional mismatch repair deficiency), MSH2( Lynch syndrome, constitutional mismatch repair deficiency), MSH3 (MSH3-associated polyposis), MSH6 (Lynch syndrome, constitutional mismatch repair deficiency), MUTYH (MUTYH-associated polyposis), NBN (Nijmegen chromosomal instability syndrome, breast cancer susceptibility), NF1 (neurofibromatosis type 1), NF2 (neurofibromatosis type 2), NTHL1 (NTHL1 tumor syndrome, NTHL1-associated polyposis), PALB2 (breast cancer susceptibility, pancreatic cancer susceptibility, ovarian cancer susceptibility, Fanconi anemia), PDGFRA (familial gastrointestinal stromal tumor, GIST-plus syndrome), PHOX2B (neuroblastoma susceptibility), PMS2 (Lynch syndrome, constitutional mismatch repair deficiency), POLD1 (polymerase proofreading-associated polyposis), POLE (polymerase proofreading-associated polyposis), PRKAR1A (Carney complex),PTCH1 (Gorlin syndrome, basal cell nevus syndrome), PTEN (PTEN hamartoma tumor syndrome), RAD51C (ovarian cancer susceptibility, breast cancer susceptibility, Fanconi anemia), RAD51D (ovarian cancer susceptibility, breast cancer susceptibility), RB1 (retinoblastoma), RET (multiple endocrine neoplasia type 2, familial medullary thyroid carcinoma), RUNX1 (acute myeloid leukemia susceptibility), SDHA (hereditary paraganglioma-pheochromocytoma syndrome), SDHAF2 (hereditary paraganglioma-pheochromocytoma syndrome), SDHB (hereditary paraganglioma-pheochromocytoma syndrome), SDHC (hereditary paraganglioma-pheochromocytoma syndrome) , SDHD (hereditary paraganglioma-pheochromocytoma syndrome), SMAD4 (juvenile polyposis, hereditary hemorrhagic telangiectasia), SMARCA4 (rhabdoid tumor predisposition syndrome), SMARCB1 (rhabdoid tumor predisposition syndrome, schwannomatosis), STK11 (Peutz-Jeghers syndrome), SUFU (Gorlin syndrome, basal cell nevus syndrome), TMEM127 (hereditary paraganglioma-pheochromocytoma syndrome), TP53 (Li-Fraumeni syndrome), TSC1 (tuberous sclerosis complex), TSC2 (tuberous sclerosis complex), VHL (von Hippel-Lindau disease), and WT1 (WT1-associated Wilms tumor).

[0228] In some embodiments of the disclosed method for preventing and / or reducing metastasis, next-generation sequencing can comprise the sequencing of one or more cancer-related genes.In some embodiments of the disclosed method for preventing and / or reducing metastasis, the sequencing of one or more cancer-related genes can comprise identifying one or more genomic abnormalities.In some embodiments, one or more genomic abnormalities can comprise somatic genomic abnormalities.In some embodiments, the disclosed one or more somatic genomic abnormalities can comprise mutation, insertion, deletion, chromosome rearrangement, copy number abnormality, or any combination thereof.

[0229] In some embodiments of the disclosed method for preventing and / or reducing metastasis, the disclosed cfDNA analysis can include quantifying one or more cancer-related genes.In some embodiments, if the expression and / or amount and / or presence of one or more disclosed genomic abnormalities in biological samples before treatment is greater than the expression and / or amount and / or presence of the same one or more genomic abnormalities in control samples, the disclosed method for preventing and / or reducing metastasis can include diagnosing the subject as needing high-precision cancer treatment.In some embodiments, the disclosed control sample can be a sample obtained from a subject without cancer.In some embodiments, the disclosed control sample can be a pooled sample obtained from more than one subject without cancer.

[0230] In certain embodiments, if the expression and / or amount and / or presence of one or more disclosed genomic abnormalities in a post-treatment biological sample is less than the expression and / or amount and / or presence of the same one or more genomic abnormalities in a pre-treatment sample, the disclosed methods for preventing and / or reducing metastasis can include continuing to administer a disclosed high-precision cancer treatment to the subject. In certain embodiments, if the expression and / or amount and / or presence of one or more disclosed genomic abnormalities in a post-treatment biological sample is less than the expression and / or amount and / or presence of the same one or more genomic abnormalities in a previous post-treatment sample, the disclosed methods for preventing and / or reducing metastasis can include continuing to administer a disclosed high-precision cancer treatment to the subject.

[0231] In certain embodiments, the disclosed methods of preventing and / or reducing metastasis may further include measuring the subject's tumor response to the cancer treatment with high precision. In certain embodiments, the subject's tumor response may include a partial response or a complete response. In certain embodiments, the disclosed partial response may include a 25% or greater reduction or shrinkage in tumor size or one or more tumors compared to the same tumor size or the same tumor(s) before treatment. In certain embodiments, the disclosed partial response may include a 50% or greater reduction or shrinkage in tumor size or one or more tumors compared to the same tumor size or the same tumor(s) before treatment. In certain embodiments, the disclosed partial response may include a 100% or greater reduction or shrinkage in tumor size or one or more tumors compared to the same tumor size or the same tumor(s) before treatment.

[0232] In certain embodiments, the disclosed methods for preventing and / or reducing metastasis may further comprise measuring a subject's molecular response to a disclosed high-precision cancer treatment. In certain embodiments, the disclosed molecular response may comprise a reduction in the number of somatic genomic abnormalities in a disclosed biological sample obtained from the subject. In certain embodiments, the disclosed somatic genomic abnormalities may comprise mutations, insertions, deletions, chromosomal rearrangements, copy number abnormalities, fusions, or any combination thereof. In certain embodiments, the disclosed methods for preventing and / or reducing metastasis may further comprise administering one or more additional therapeutic agents to the subject.

[0233] In certain aspects, the disclosed additional therapeutic agents can include a chemotherapeutic agent, a monoclonal antibody, a cell cycle inhibitor, a small molecule, or any combination thereof.

[0234] Monoclonal antibodies are known to those skilled in the art and may include, but are not limited to, adotrastuzumab, alemtuzumab, atezolizumab, avelumab, bevacizumab, blinatumomab, brentuximab, cemiplimab, cetuximab, daratumumab, denosumab, dinutuximab, durvalumab, elotuzumab, gemtuzumab, ibritumomab, inotuzumab, ipilimumab, necitumumab, nivolumab, obinutuzumab, ofatumumab, olaratumumab, panitumumab, pembrolizumab, pertuzumab, ramucirumab, rituximab, tositumomab, trastuzumab, or any combination thereof.

[0235] Small molecules are known to those skilled in the art. Examples of small molecules include abemaciclib, afatinib, alectinib, alpelisib, axitinib, binimetinib, bosutinib, brigatinib, cabozantinib, carfilzomib, ceritinib, gilteritinib (cgilteritinib), cobimetinib, copanlisib, crizotinib, dabrafenib, dacomitinib, dasatinib, duvelisib, encorafenib, entrectinib, erdafitinib, erlotinib, gefitinib, and ibromidine. These may include, but are not limited to, rutinib, imatinib, ivosidenib, lapatinib, larotrectinib, lenvatinib, lorlatinib, marizomib, neratinib, nilotinib, niraparib, olaparib, osimertinib, palbociclib, pazopanib, ponatinib, regorafenib, ribociclib, rucaparib, sorafenib, sunitinib, talazoparib, trametinib, vandetanib, vemurafenib, or any combination thereof. In some embodiments, the additional therapeutic agent may include bevacizumab, pazopanib, sorafenib, dasatinib, everolimus, or any combination thereof.

[0236] For example, in some embodiments, pazopanib and / or sorafenib can be orally administered to a subject at a dose of about 1 mg / kg / day to about 12 mg / kg / day, or 2 mg / kg / day to about 6 mg / kg / day. In some embodiments, the disclosed optimal dose of pazopanib and / or sorafenib can be about 3 mg / kg / day. In some embodiments, dasatinib can be orally administered to a subject at a dose of about 0.3 mg / kg / day to about 2.0 mg / kg / day, or about 0.7 mg / kg / day to about 1.4 mg / kg / day. In some embodiments, the disclosed optimal dose of dasatinib can be about 0.7 mg / kg / day. In some embodiments, everolimus can be orally administered to a subject at a dose of about 0.03 mg / kg / day to about 0.15 mg / kg / day, or about 0.03 mg / kg / day to about 0.10 mg / kg / day. In some embodiments, the disclosed optimal dose of everolimus can be about 0.07 mg / kg / day. In some embodiments, bevacizumab can be administered intravenously to a subject at a dose of about 2 mg / kg / day to about 15 mg / kg / day every 1-3 weeks, or at a dose of about 5 mg / kg / day to about 12 mg / kg / day every 1-3 weeks. In some embodiments, the disclosed optimal dose of bevacizumab can be administered intravenously to a subject at an optimal dose of about 10 mg / kg / day every 2 weeks.

[0237] In certain embodiments, the disclosed molecular markers that may determine one or more appropriate high-precision cancer treatments in one or more disclosed methods can be measured from a sample by high-density expression arrays, DNA microarrays, polymerase chain reaction (PCR), reverse transcriptase PCR (RT-PCR), real-time quantitative reverse transcription PCR (qRT-PCR), serial analysis of gene expression (SAGE), spotted cDNA arrays, GeneChips, spotted oligo arrays, bead arrays, RNA-Seq, tiling arrays, Northern blotting, hybridization microarrays, in situ hybridization, whole exome sequencing, whole genome sequencing, liquid biopsy, next-generation sequencing, or any combination thereof.

[0238] In some embodiments, the disclosed molecular markers can determine one or more appropriate high-precision cancer treatments for use in the disclosed methods for preventing and / or reducing metastasis, and can be determined from at least one nucleic acid sequence of circulating DNA and / or RNA. In some embodiments, the disclosed molecular markers can be evaluated from circulating tumor DNA and / or RNA (ctDNA and / or ctRNA); circulating cell-free DNA and / or RNA (cfDNA, cfRNA); or any combination thereof. ctDNA / ctRNA refers to fragmented DNA derived from tumors in the bloodstream that is not associated with cells. cfDNA / cfRNA refers to DNA that circulates freely in the bloodstream but does not necessarily originate from tumors. In some embodiments, cfDNA / ctDNA can include any whole or fragmented genomic DNA or mitochondrial DNA, and / or cfRNA / ctRNA can include mRNA, tRNA, microRNA, small interfering RNA, and long non-coding RNA (ncRNA). In some embodiments, cfDNA and / or ctDNA can be fragmented DNA with a length of at least about 50 base pairs (bp), about 100bp, about 200bp, about 500bp, or about 1 kbp. In some embodiments, cfRNA and / or ctRNA can be full-length or fragments of mRNA (e.g., at least 70% of full length, at least 50% of full length, at least 30% of full length, etc.). In some embodiments, the disclosed molecular markers can be targeted to any cancer-related gene disclosed herein.

[0239] In certain aspects, the disclosed methods of preventing and / or reducing metastasis may further comprise surgically removing one or more tumors from the subject. In certain aspects, the disclosed methods of preventing and / or reducing metastasis may further comprise repeating one or more of the disclosed steps of the disclosed methods.

[0240] For example, in certain aspects, repeating one or more disclosed steps of the disclosed methods of preventing and / or reducing metastasis can include repeating administering a precision cancer treatment to the subject, repeating measuring the subject's tumor response, repeating obtaining a biological sample from the subject, repeating subjecting the biological sample to cfDNA analysis, repeating administering one or more additional therapeutic agents, or any combination thereof.

[0241] In certain embodiments, the disclosed molecular markers can be detected, quantified, and / or analyzed over time (at various time points) to determine the effect of the disclosed precision cancer treatments (e.g., AS treatment) on a subject and / or to determine the response of the subject or the subject's tumor to the precision cancer treatment (e.g., development of resistance, susceptibility, etc.). In certain embodiments, the disclosed methods of preventing and / or reducing metastasis can include obtaining multiple measurements from the same subject over time, and the same sample can be quantified at a single time point or over time. In certain embodiments, treatment with the disclosed treatment regimens (e.g., the disclosed precision cancer treatments comprising one or more antineoplastons) can be designed and / or determined based on the state of the cancer and / or the alteration / type of one or more molecular markers. In certain embodiments, the likelihood of success of the disclosed precision cancer treatments can be determined based on the state of the cancer and the type / quantity of one or more molecular markers.

[0242] In some embodiments, the disclosed molecular markers may be derived from genes expressed in one or more cells of a tumor or in immune cells, and may indicate an immunosuppressive tumor microenvironment, the occurrence of cancer stemness, the onset of metastasis, the state of cancer, or any combination thereof. In some embodiments, the disclosed molecular markers may be proteins or peptides encoded by the genes from which the molecular markers are derived, and can be targeted by antagonists or any other type of binding molecules to inhibit the function of the peptides.

[0243] Thus, in certain embodiments, increased expression (e.g., above a predetermined threshold) of the disclosed molecular markers derived from the disclosed genes associated with an immunosuppressive tumor microenvironment can be associated with the presence of an immunosuppressive tumor microenvironment, and can be associated with the fact that antagonists against peptides encoded by genes associated with an immunosuppressive tumor microenvironment may have a high probability of success in inhibiting the immunosuppressive tumor microenvironment and further promoting immune cell activity against tumor cells within such a microenvironment, thereby inhibiting cancer progression. In certain embodiments, once a molecular marker is identified, any appropriate antagonist against the target gene or protein product can be used. For example, in certain embodiments, a specific kinase can be targeted by a kinase inhibitor, or a specific signaling receptor can be targeted by a synthetic ligand, or a specific checkpoint receptor can be targeted by a synthetic antagonist or antibody, etc. In certain embodiments, the disclosed antagonists against the target molecules herein can be administered before, after, or in combination with AS treatment.

[0244] In some embodiments, the subject may be a human patient. In some embodiments, the subject may be of any age (e.g., elderly, adult, young adult, teenager, tween, adolescent, child, toddler, infant, or newborn), male or female, of any nationality, any ethnicity, and / or any race. In some embodiments, the subject may have terminal cancer.

[0245] In some embodiments, the disclosed subject has not received treatment prior to administration of the disclosed precision cancer treatment. In some embodiments, the disclosed subject has received treatment prior to administration of the disclosed precision cancer treatment. In some embodiments of the disclosed methods of preventing and / or reducing metastasis, the subject has received surgery, antibody treatment, chemotherapy treatment, radiation treatment, immunotherapy treatment, or any combination thereof prior to administration of the disclosed precision cancer treatment. In some embodiments of the disclosed methods of preventing and / or reducing metastasis, the subject in need thereof has been diagnosed with cancer, or the subject in need thereof is suspected of having cancer.

[0246] In certain embodiments, the disclosed cancers may be refractory cancers or refractory diseases. In certain embodiments, "refractory" refers to cancers and / or tumors that do not respond to treatment and / or become resistant to treatment. In certain embodiments, the subject may have relapsed disease. In certain embodiments, "relapsed" or "relapse" refers to a tumor that returns or progresses after a period of improvement with treatment (e.g., partial or complete response). In certain embodiments, the disclosed cancers may include solid tumors. In certain embodiments, the disclosed cancers may include metastatic cancers. In certain embodiments, the disclosed cancers may include terminal cancers.

[0247] In certain embodiments, the disclosed cancers include adenocarcinomas (including those of the adnexa and cervix), adenoid cystic carcinoma, adult T-cell leukemia, anaplastic astrocytoma, anaplastic ependymoma, anaplastic oligodendroglioma, astrocytoma, basal cell carcinoma, B-cell carcinoma, benign and malignant lymphoma, biliary tract-cholangiocarcinoma, intestine, brain cancers (anaplastic astrocytoma, anaplastic ependymoma, anaplastic oligodendroglioma, brainstem anaplastic astrocytoma, brainstem glioma, diffuse astrocytoma, DIPG, h3k27 mutation, ganglioglioma, glioblastoma multiforme, medulloblastoma, pilocytic astrocytoma, brainstem glioma), breast cancer, Burkitt's lymphoma, bladder cancer and bladder cancer, carcinoma of unknown primary, carcinosarcoma, cervical cancer, cholangiocarcinoma, chronic atypical myeloid leukemia, chronic atypical myeloid leukemia, colon cancer, colorectal cancer, diffuse astrocytoma, diffuse intrinsic pontine glioma (DIPG), uterine cancer, endometrial cancer, ependymoma, esophageal cancer and esophageal cancer, euthyroid Ing's sarcoma, ganglioglioma, ganglioneuroma, gastrointestinal stromal tumor (gist), glioblastoma, glioma, head and neck cancer, angiosarcoma, hepatocellular carcinoma, renal cell carcinoma, Hodgkin's disease, Kaposi's sarcoma, kidney cancer and renal carcinoma, large B-cell lymphoma, leptomeningeal carcinomatosis, leukemia, liposarcoma, liver cancer, lung cancer (non-small cell and small cell carcinoma), medulloblastoma, melanoma, meningeal sarcoma, meningioma, multiple myeloma, myelodysplastic syndrome, myeloproliferative disorders, muscle tumor, neuroblastoma, neuroendocrine carcinoma, neurofibroma, non-Hodgkin's lymphoma, oligodendroglioma, osteosarcoma, ovarian cancer and ovarian cancer, pancreatic cancer and pancreatic cancer, peripheral neuroepithelioma, peripheral T-cell lymphoma, Philadelphia chromosome positive ALL and positive CML, pilocytic astrocytoma, pineal cell tumor, pleomorphic sarcoma, pre-B cell lymphoma, primitive neuroectodermal tumor (PNET), prostate cancer and prostate cancer, refractory anemia, salivary gland cancer, sarcoma tumors, schwannoma, skin cancer and skin cancer, squamous cell carcinoma, gastric cancer and gastric cancer, synovial sarcoma, testicular cancer, thyroid cancer and thyroid cancer, T-lineage acute lymphoblastic leukemia (T-all), T-lineage lymphoblastic lymphoma (T-LL), urothelial cancer and high-grade urothelial carcinoma, uterine cancer, cervical cancer, vulvar cancer, and / or endometrial cancer, Wilms' tumor or teratocarcinoma, or any combination thereof.

[0248] In certain aspects, the disclosed cancers include breast cancer, colorectal cancer, head and neck cancer, kidney cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, brain cancer, adenoid cystic carcinoma, anaplastic astrocytoma, anaplastic ependymoma, anaplastic oligodendroglioma, brain stem glioma, diffuse astrocytoma, diffuse intrinsic pontine glioma (DIPG), ganglioglioma, medulloblastoma, pilocytic astrocytoma, cholangiocarcinoma, chronic atypical myeloid leukemia, endometrial cancer, esophageal cancer, Ewing's sarcoma, gastrointestinal stromal tumor (GIST), leptomeningeal carcinomatosis, multiple myeloma, myelodysplastic syndrome, neuroendocrine carcinoma, non-Hodgkin's lymphoma, pleomorphic sarcoma, primitive neuroectodermal tumor (PNET), refractory anemia, salivary gland cancer, skin cancer, stomach cancer, The cancers may include thyroid cancer, urothelial cancer, or any combination thereof.

[0249] In certain embodiments, the disclosed methods of preventing and / or reducing metastasis may further comprise monitoring the subject for adverse effects (e.g., liver dysfunction, hematologic toxicity, neurotoxicity, skin toxicity, gastrointestinal toxicity, or any combination thereof). In certain embodiments, in the absence of adverse effects, the disclosed methods of preventing and / or reducing metastasis may further comprise continuing to administer the disclosed high-precision cancer treatment to the subject. In certain embodiments, in the presence of adverse effects, the disclosed methods of preventing and / or reducing metastasis may further comprise modifying one or more disclosed steps of the disclosed methods. In certain embodiments, the disclosed methods of preventing and / or reducing metastasis may further comprise treating one or more adverse effects.

[0250] In certain embodiments, the disclosed methods of preventing and / or reducing metastasis can include modifying the disclosed administering step. In certain embodiments, the disclosed modifying the administering step can include changing the amount of one or more antineoplastons or compositions comprising one or more antineoplastons administered to a subject, changing the frequency with which one or more antineoplastons or compositions comprising one or more antineoplastons are administered to a subject, changing the duration of administration of one or more antineoplastons or compositions comprising one or more antineoplastons, changing the route of administration of one or more antineoplastons or compositions comprising one or more antineoplastons administered to a subject, or any combination thereof.

[0251] In certain embodiments, the disclosed methods for preventing and / or reducing metastasis may further include obtaining a tissue biopsy from a subject. In certain embodiments, the disclosed tissue biopsy may be subjected to next-generation sequencing. In certain embodiments, the disclosed methods for preventing and / or reducing metastasis may include subjecting the subject to one or more invasive or non-invasive diagnostic evaluations. Diagnostic evaluations are known in the art. In certain embodiments, the disclosed non-invasive diagnostic evaluations may include X-rays, computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, ultrasound, positron emission tomography (PET) scans, or any combination thereof. In certain embodiments, the disclosed invasive diagnostic evaluations may include tissue biopsies or exploratory surgery.

[0252] In some embodiments, the disclosed subject may have an improved life expectancy. In some embodiments, the subject's life expectancy is compared with that of a control. In some embodiments, the control is a subject who has not undergone high-precision cancer treatment. In some embodiments, the control is a pooled number of subjects who have not undergone high-precision cancer treatment. In some embodiments, the control is one or more subjects with the same type and stage of cancer as the subject. In some embodiments of the disclosed methods for preventing and / or reducing metastasis, the subject's cancer is treated.

[0253] In certain embodiments, the disclosed methods of preventing and / or reducing metastasis may improve life expectancy compared to the life expectancy of an untreated subject with cancer who has the same or nearly the same disease state and the same or nearly the same predicted outcome. As used herein, "life expectancy" is defined as the point at which 50 percent of subjects are alive and 50 percent are dead. In certain embodiments, a patient's life expectancy after treatment with the disclosed methods may be indefinite. In certain embodiments, a patient's life expectancy may be increased by at least about 5% or more to at least about 100%, by at least about 10% or more to at least about 95% or more, by at least about 20% or more to at least about 80% or more, or by at least about 40% or more to at least about 60% or more compared to an untreated subject with the same or nearly the same disease state and the same or nearly the same predicted outcome.

[0254] In certain embodiments, life expectancy may be increased by at least about 5% or more, at least about 10% or more, at least about 15% or more, at least about 20% or more, at least about 25% or more, at least about 30% or more, at least about 35% or more, at least about 40% or more, at least about 45% or more, at least about 50% or more, at least about 55% or more, at least about 60% or more, at least about 65% or more, at least about 70% or more, at least about 75% or more, at least about 80% or more, at least about 85% or more, at least about 90% or more, at least about 95% or more, or at least about 100% compared to an untreated subject with the same or approximately the same disease state and the same or approximately the same predicted outcome.In certain embodiments, life expectancy is at least about 5% or more to at least about 10% or more, at least about 10% or more to at least about 15% or more, at least about 15% or more to at least about 20% or more, at least about 20% or more to at least about 25% or more, at least about 25% or more to at least about 30% or more, at least about 30% or more to at least about 35% or more, at least about 35% or more to at least about 40% or more, at least about 40% or more to at least about 45% or more, at least about 45% or more to at least about 50% or more, compared to untreated patients with the same or nearly the same disease state and the same or nearly the same predicted outcome. % or more, at least about 50% or more to at least about 55% or more, at least about 55% or more to at least about 60% or more, at least about 60% or more to at least about 65% or more, at least about 65% or more to at least about 70% or more, at least about 70% or more to at least about 75% or more, at least about 75% or more to at least about 80% or more, at least about 80% or more to at least about 85% or more, at least about 85% or more to at least about 90% or more, at least about 90% or more to at least about 95% or more, at least about 95% or more to at least about 100% extended.

[0255] In some embodiments, the disclosed methods for preventing and / or reducing metastasis may include protecting a subject from metastasis. In some embodiments, the disclosed methods for preventing and / or reducing metastasis may include reducing the risk of developing metastasis. In some embodiments of the disclosed methods for preventing and / or reducing metastasis, treating cancer may include increasing the subject's chances of survival, increasing the length of time before metastasis, reducing the likelihood of surgical intervention, reducing the need to administer one or more additional therapeutic agents or regimens, reducing the size of one or more tumors in a subject, eliminating one or more tumors in a subject, reducing or eliminating the prevalence of one or more genomic abnormalities, restoring normal metabolism in one or more organ systems in a subject, restoring one or more aspects of cellular homeostasis and / or cellular functionality, and / or metabolic dysregulation, or any combination thereof.

[0256] In certain embodiments of the disclosed methods of preventing and / or reducing metastasis, restoring one or more aspects of cellular homeostasis and / or cellular functionality may include one or more of the following: (i) correcting cellular starvation in one or more cell types (e.g., hepatocytes and muscle cells, etc.); (ii) normalizing aspects of the autophagy pathway (e.g., correcting, preventing, reducing, and / or reversing autophagy, etc.); (iii) improving, enhancing, restoring, and / or preserving mitochondrial functionality and / or structural integrity; and (iv) organelles. (v) preventing, slowing, and / or eliminating hypoglycemia, ketosis, and / or other liver abnormalities, (vi) correcting liver enzyme dysregulation, (vii) reversing, inhibiting, preventing, stabilizing, and / or slowing tumor metastasis, (viii) reversing, inhibiting, preventing, stabilizing, and / or slowing tumor growth and / or cancer spread, or (ix) any combination thereof. In certain embodiments, restoring one or more aspects of cellular homeostasis can include, for example, improving, enhancing, restoring, and / or preserving one or more aspects of the structural and / or functional integrity of cells in an organ or system affected by cancer.

[0257] For example, in certain embodiments, tumor growth may be reduced by at least about 5% or more to at least about 100%, at least about 10% or more to at least about 95% or more, at least about 20% or more to at least about 80% or more, at least about 40% or more to at least about 60% or more, compared to an untreated subject with the same or nearly the same disease state and the same or nearly the same predicted outcome. In certain embodiments, one or more tumors in a subject treated using the disclosed methods for preventing and / or reducing metastasis may grow at least 5% (or more, as described above) less than an untreated subject with the same or nearly the same disease state and the same or nearly the same predicted outcome.

[0258] In certain embodiments, tumor growth may be reduced by at least about 5% or more, at least about 10% or more, at least about 15% or more, at least about 20% or more, at least about 25% or more, at least about 30% or more, at least about 35% or more, at least about 40% or more, at least about 45% or more, at least about 50% or more, at least about 55% or more, at least about 60% or more, at least about 65% or more, at least about 70% or more, at least about 75% or more, at least about 80% or more, at least about 85% or more, at least about 90% or more, at least about 95% or more, or at least about 100% compared to an untreated subject with the same or approximately the same disease state and the same or approximately the same predicted outcome.

[0259] In certain embodiments, tumor growth is at least about 5% or more to at least about 10% or more, at least about 10% or more to at least about 15% or more, at least about 15% or more to at least about 20% or more, at least about 20% or more to at least about 25% or more, at least about 25% or more to at least about 30% or more, at least about 30% or more to at least about 35% or more, at least about 35% or more to at least about 40% or more, at least about 40% or more to at least about 45% or more, at least about 45% or more to at least about 50% or more, or It may be reduced by 0% or more, at least about 50% or more to at least about 55% or more, at least about 55% or more to at least about 60% or more, at least about 60% or more to at least about 65% or more, at least about 65% or more to at least about 70% or more, at least about 70% or more to at least about 75% or more, at least about 75% or more to at least about 80% or more, at least about 80% or more to at least about 85% or more, at least about 85% or more to at least about 90% or more, at least about 90% or more to at least about 95% or more, at least about 95% or more to at least about 100%.

[0260] In certain embodiments, treatment of a tumor according to the methods disclosed herein (e.g., AS treatment) can result in tumor shrinkage compared to the size of the tumor at the start of treatment. In certain embodiments, tumor shrinkage can be at least about 5% or more to at least about 10% or more, at least about 10% or more to at least about 15% or more, at least about 15% or more to at least about 20% or more, at least about 20% or more to at least about 25% or more, at least about 25% or more to at least about 30% or more, at least about 30% or more to at least about 35% or more, at least about 35% or more to at least about 40% or more, at least about 40% or more to at least about 45% or more, at least about 45% or more to at least about 50% or more, or at least about 50% or more compared to the size of the tumor at the start of treatment. or more to at least about 55% or more, at least about 55% or more to at least about 60% or more, at least about 60% or more to at least about 65% or more, at least about 65% or more to at least about 70% or more, at least about 70% or more to at least about 75% or more, at least about 75% or more to at least about 80% or more, at least about 80% or more to at least about 85% or more, at least about 85% or more to at least about 90% or more, at least about 90% or more to at least about 95% or more, at least about 95% or more to at least about 100% (i.e., complete disappearance of the tumor following treatment).

[0261] In certain embodiments, the disclosed subject may exhibit one or more cancerous solid tumors, metastatic lymph nodes, or any combination thereof. In any embodiment, a subject herein may have a cancerous tumor cell source that may be less than about 0.2 cm to at least about 20 cm or larger, at least about 2 cm to at least about 18 cm or larger, at least about 3 cm to at least about 15 cm or larger, at least about 4 cm to at least about 12 cm or larger, at least about 5 cm to at least about 10 cm or larger, or at least about 6 cm to at least about 8 cm or larger.

[0262] In certain embodiments, the disclosed methods of preventing and / or reducing metastasis can include a pan-tumor approach, such as, for example, administering the disclosed ANP treatments.

[0263] F. Kit Disclosed herein are kits comprising one or more of the disclosed antineoplastons, the disclosed pharmaceutical formulations, or any combination thereof. In certain embodiments, the kits can include the disclosed pharmaceutical formulations comprising one or more antineoplastons, one or more additional active agents and / or therapeutic agents, or any combination thereof. "Active agents" and "therapeutic agents" are known in the art and are described above.

[0264] In certain embodiments, the one or more active agents may treat, prevent, inhibit, and / or ameliorate one or more co-morbidities in a subject. In certain embodiments, the one or more active agents may treat, inhibit, prevent, and / or ameliorate cancer or cellular and / or metabolic complications associated with cancerous or cancerous cells.

[0265] In certain embodiments, the disclosed kits may include at least two components that make up the kit. The components, together, form a functional unit for a given purpose (e.g., treating a subject diagnosed with or suspected of having a disease or disorder, such as cancer). The individual member components may be physically packaged together or separately. For example, a kit including instructions for use of the kit may or may not physically include the instructions associated with the other individual member components. Alternatively, the instructions may be provided as a separate member component, either in paper form, or in electronic form that may be provided on a computer-readable memory device or downloadable from an internet website, or as a recorded display. In certain embodiments, kits for use in the disclosed methods may include one or more containers holding one or more of the disclosed antineoplastons, the disclosed pharmaceutical formulations, one or more therapeutic and / or additional agents, or any combination thereof, as well as a label or package insert with instructions for use. In certain embodiments, suitable containers include, for example, bottles, vials, syringes, blister packs, etc. The container may be formed from a variety of materials, such as glass or plastic. The container may hold one or more of the disclosed antineoplastons, the disclosed pharmaceutical formulations, or any combination thereof, and may have a sterile access port (e.g., the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic injection needle). The label or package insert may indicate that the one or more of the disclosed antineoplastons, the disclosed pharmaceutical formulations, or any combination thereof can be used to treat, prevent, inhibit, and / or ameliorate a disease or disorder or complications and / or symptoms associated with the disease or disorder, such as cancer or metastatic cancer. The kit may include additional components necessary for administration, such as other buffers, diluents, filters, needles, and syringes.

[0266] In certain embodiments, the disclosed kits can be used to treat and / or prevent cancer, prolong survival, prevent and / or reduce metastasis, or any combination thereof. [Example]

[0267] VI. Working Examples Example 1 Patients diagnosed with 34 types of terminal cancer were treated with antineoplaston AS2-1 (AS) therapy to reduce and / or eliminate tumors and other signs of cancer, as well as to reduce and / or eliminate the expression of cancer-causing genes. Briefly, patients accepted for treatment herein were diagnosed with various types of terminal, stage IV, multimetastatic cancer and had failed standard treatment regimens, with the exception of a small number of treatment-naive patients who were not candidates for standard treatment due to their highly advanced disease and life expectancy of less than six months. These patients had estimated survival ranging from less than one month to less than six months. Patients had radiological evidence of advanced metastatic cancer performed within four weeks of treatment initiation and genomic analysis, usually ordered at the time of admission, including Guardant 360 blood testing and / or Foundation One and / or Tempus blood or tissue testing and / or SEMA4 tissue testing. Histological confirmation of diagnosis was performed at a medical institution unaffiliated with the Burzynski Clinic (BC).

[0268] Patients received anticancer treatment with AS and A10 (ANP) along with targeted, immunological, hormonal, and / or chemotherapeutic agents. In some cases, palliative radiation therapy (RT) and / or surgery were used in addition to the anticancer drugs. ANP was delivered every 4 hours via a portable infusion pump and subclavian catheter. The AS dose was gradually increased from 0.1 g / kg / day at a flow rate of 50 mL / hour to 250 mL / hour, up to a maximum of 0.4 g / kg / day after 4 days. The A10 dose was increased up to a maximum of 12 g / kg / day. The majority of patients continued treatment with the best tolerated doses of 0.2–0.4 g / kg / day AS and 5 g / kg / day A10 at a flow rate of 200–250 mL / hour.

[0269] Medications deemed necessary for the patient's well-being and that did not interfere with the treatment were prescribed at the discretion of the treating physician. Patients received adequate supportive care and dietary advice. Treatment was performed on an outpatient basis in collaboration with the patient's local physician.

[0270] At baseline, a medical history, physical examination, and necessary clinical, genomic, and radiological evaluations were performed. Measurements of the two perpendicular longest diameters of radiologically significant lesions, including MRI contrast-enhancing lesions in the brain and spinal cord, were performed. Responses were determined using follow-up scans, usually at 4- to 8-week intervals. A complete response (CR) required the disappearance of all enhancing lesions and stable or improving nonenhancing lesions, as well as the disappearance of lesions outside the target tissue by CT or metabolically active lesions by PET. A partial response (PR) required a 50% or greater reduction in the sum of the products of the two perpendicular longest diameters of the lesions, and progressive disease (PD) was defined as an increase of more than 25%. Stable disease (SD) was a state between PR and PD, and a minor response (MR) was defined as a reduction of more than 25%. A mixed response was defined as a CR or PR and PD in some lesions.

[0271] In clinical trials, CR and PR should last at least 4 weeks, and SD should last at least 7 weeks. In private practice, some patients did not consent to follow-up radiological evaluation due to radiation exposure or additional costs. In such cases, response was considered CR. * or PR * Some patients with multiple organ metastases achieved CR or PR in one organ, e.g., the liver, but not in others. These patients were noted as CR (HEP) and SD (OSS), as appropriate, meaning CR in the liver and SD in the bone.

[0272] Molecular response was determined by repeating Guardant 360 testing. Briefly, Guardant 360 testing generally involves cell-free circulating tumor DNA (ctDNA) panel testing from blood (e.g., plasma) samples, as an alternative to tissue biopsy in cancer diagnosis and for clinical response to targeted agents in cancer treatment. Here, blood samples are collected from patients and provided to Guardant for panel testing. Here, "panel" is defined as five or more ctDNA genes or gene mutation variants tested by the same member on the same day by the same rendering provider (i.e., Guardant).

[0273] Treatment plans were developed based on an evaluation, including the patient's medical history and genomic data. All patients were treated with AS, which covers 158 abnormal genes, plus an additional targeted drug that acts on genes not affected by AS. The genes affected by AS and A10 are listed in Table 1. In some cases, a milder form of chemotherapy was used initially to accelerate response, and for some patients, A10 was added. [Table 1]

[0274] The goal of treatment is to achieve CR and complete disappearance of the abnormal gene from the patient's blood.At this point, the patient is encouraged to continue treatment for up to 8 months, and CR is monitored by radiological evaluation, preferably once every 8 weeks, and blood genomic testing every 3 months.This representative example only includes evaluable patients who have undergone recommended radiological and genomic follow-up evaluation.

[0275] The results of this study are described herein in three parts: Part 1 describes the results in common cancers, Part 2 describes the results in less common cancers, and Part 3 summarizes the results in all evaluable patients.

[0276] The following abbreviations are used herein: am (amplification); AS (antineoplaston AS2-1); BC (Burzynski Clinic, site of the study reported herein); BRA (brain metastases); CH (chemotherapy); CR (complete response); CR * (complete response not confirmed by follow-up scan); DAMA (discontinued against medical advice); Dd (patients who died under treatment due to malignancy); De (patients who died under treatment due to any cause other than malignancy); Dx (patients who died under treatment but the cause was not recorded); DEPB (dasatinib, everolimus, pazopanib, bevacizumab); DESB (dasatinib, everolimus, sorafenib, bevacizumab); ER+ (estrogen positive); GBM (glioblastoma, glioblastoma multiforme); H (hormonal treatment); HER-2 - (HER-2 - negative);HER-2 +(HER-2 positive); IM (improvement); LMN (leptomeningeal metastasis); LYM (lymph node metastasis); MR (minor response); ND (not detectable); OR (objective response); OS (overall survival from start of treatment); OSS (bone metastasis); PE (physical examination); PR (partial response); PR+ (progesterone positive); PUL (lung metastasis); RT (radiotherapy); SKI (skin metastasis); SU (surgery, the number in front indicates the number of times); TN BC (triple-negative breast cancer); and TT (targeted therapy, the target of TT is in parentheses).

[0277] Part I - Common Cancers Breast cancer. Nineteen patients with a diagnosis of advanced, late-stage breast cancer were eligible for inclusion in this study. All patients were women, and the age range was 51 to 65 years (11 patients) and 38 to 48 years (8 patients). Patients were divided into three groups: 11 in the HER-2-negative group, 2 in the triple-negative group, and 6 in the HER-2-positive group. One patient had a heterogeneous population of cancer cells, with some HER-2-negative and some HER-2-positive. Ten patients had long-term disease duration, ranging from 4 to 16 years, while nine patients had disease duration ranging from 1 to 3 years. All patients had failed multiple treatment regimens, including surgery, radiation, chemotherapy, and hormonal therapy and / or targeted therapy. The exception was one patient who was treatment-naive because she was near death and was not a candidate for standard treatment. Patients had widespread metastatic disease, including involvement of the brain, meninges, bone, liver, lung, lymph nodes, pleura, peritoneum, ovaries, skin, thyroid, and contralateral breast. Estimated survival was 1 to 3 months in 11 patients and less than 6 months in 8 patients.

[0278] Five patients had received prior treatment with surgery, radiation therapy, chemotherapy, and hormone therapy; five patients had received prior treatment with surgery, radiation, and chemotherapy; three patients had received prior treatment with surgery, radiation, and hormone therapy; and one patient had received prior treatment with radiation, chemotherapy, hormone therapy, and targeted therapy. Eight patients had received targeted therapy; one patient had received surgery and targeted therapy. Three patients had received multiple surgeries, and another two had received multiple types of radiation therapy. Five patients had received multiple chemotherapy regimens, and three patients had received multiple targeted therapy regimens. Details are presented in Table 2. [Table 2-1] [Table 2-2]

[0279] Patients were treated as described above. Treatment details and results are presented in Tables 3, 4, 5, and 6. Five patients in the HER-2-negative group achieved a CR. The remaining five patients in this group achieved a PR, and one patient achieved an MR. Brain radiotherapy may have contributed to the response in two patients (Table 3). For four patients, genomic abnormalities identified at baseline were no longer found in the blood after treatment. Two patients in the triple-negative group achieved a CR, including one patient with brain and leptomeningeal involvement. Repeat Guardant360 testing no longer showed multiple mutated genes in the blood for one patient (Table 4). HER-2 +Five patients in the group achieved a CR, of which four had a radiologically confirmed CR in one organ and a different response in the other organ. One patient achieved a PR. Three patients failed to respond to previous targeted therapy with a HER-2 inhibitor but responded when such targeted therapy was combined with AS (Table 5). After treatment, all blood genomic abnormalities on the baseline Guardant 360 test were no longer present, except for the gene CCNE1, which was reduced by 85% in one case (Table 5). [Table 3-1] [Table 3-2] [Table 3-3] [Table 4] [Table 5-1] [Table 5-2] [Table 5-3] [Table 6]

[0280] Table 6 summarizes the responses in a phase 2 trial of AS and A10 in breast cancer compared with responses to previous targeted therapy. As shown in Table 6, a very high objective response rate was observed, with 12 CRs, 6 PRs, and 1 MR, and no PDs. No objective responses were observed with AS and A10 in clinical trials. There were four PDs with previous targeted therapy. Overall survival was 78.9% at 2 years and 42.1% at 3 years.

[0281] An additional group of 14 patients who were not evaluable for this report were treated under Right to Try. Four of these died of cancer and could be classified as PD, but two PRs and one MR were observed, and the patient remains alive. The addition of these seven cases increases the number of patients to 26. The following responses were observed for this expanded group: CR (12), 46.1%; PR (8), 30.7%; MR (2), 7.6%; PD (4), 15.3%; and objective response (OR) 84.7%.

[0282] Table 7 presents the genes and site mutations affected by antineoplaston AS2-1 based on clinical results for breast cancer. [Table 7]

[0283] A total of eight patients with advanced colorectal cancer were treated. This group consisted of four women and four men, ranging in age from 50 to 78 years. One patient was diagnosed with rectal adenocarcinoma, and the remaining patients were diagnosed with colon adenocarcinoma. Disease duration ranged from 3 to 7 years in four patients and less than 1 to 2 years in the remaining three. The patients had widespread metastatic disease, including four with liver, lung, and lymph node metastases and four with peritoneal metastases. Estimated survival was less than 4 months in one patient and less than 6 months in five patients. One patient had received prior treatment with surgery, radiation, chemotherapy, and targeted therapy; three patients had received surgery, chemotherapy, and targeted therapy; three additional patients had only surgery; and one had no prior treatment (Table 8). [Table 8]

[0284] Patients were treated as described above. Treatment details and results are presented in Tables 9, 10, and 11. Four patients achieved CR, two MR, and one SD. Objective responses were observed for both colon and rectal cancer patients. Table 10 summarizes the responses and compares them with responses in the Phase 2 colon cancer trials of AS and A10 and responses to previous targeted therapy. As shown in Table 10, while there were no objective responses in clinical trials or to previous targeted therapy, a very high response rate was observed for this treatment group, with four CRs, one MR, and one SD. [Table 9-1] [Table 9-2] [Table 10]

[0285] Patients showed significant improvement and decreased concentrations of mutant genomic markers in their blood, as summarized in Table 11. Pretreatment, estimated survival was less than 4-6 months. However, after treatment, survival at 4 years was 77.8%. [Table 11]

[0286] An additional group of 8 patients, not evaluable for this report, was treated under Right to Try. Of these, 4 died of cancer and were classified as PD, 4 achieved MR, 3 are alive, and 1 died of other causes. For the expanded group, the following responses were observed: CR (4), 25%; PR (0), 0%; MR (7), 43.7%; SD (1), 6.2%; PD (4), 25%; OR (12), 74.9%.

[0287] Head and Neck Cancer. A group of four patients with a diagnosis of end-stage head and neck cancer were eligible for inclusion in this study. This group consisted of three men and one woman. The duration of disease in this group ranged from 2 to 14 years, and life expectancy ranged from less than 1 month to 6 months. Patients had widespread metastatic disease involving lymph nodes, lung, pleura, liver, and bone. Pathological diagnoses for this group of patients included squamous cell carcinoma, mucoepidermoid carcinoma of the submandibular gland, and poorly differentiated acinic cell carcinoma of the parotid gland. Prior treatment included surgery, radiation, three chemotherapy regimens, and two targeted therapies; surgery, radiation, and targeted therapies; surgery, radiation, and two chemotherapy regimens; and radiation and targeted therapies (Table 12). [Table 12]

[0288] Patients were treated as described above. Details and results are presented in Tables 13, 14, and 15. One patient each achieved PR, MR, and SD, and one patient experienced PD. Genomic analysis showed activity against two mutated genes and one amplified gene (Table 15). Table 14 summarizes the response compared to previous clinical trials with AS and A10, which did not show OR, and targeted therapy. [Table 13] [Table 14] [Table 15]

[0289] Pretreatment estimated survival ranged from less than 1 month to 6 months. As a result of treatment, estimated survival increased from more than 4 months to more than 12 months, accompanied by symptomatic improvement. An additional group of two patients, not evaluable for this report, received treatment under Right to Try. Both discontinued treatment before response could be assessed. Both patients are currently alive.

[0290] Kidney Cancer. Two patients with a diagnosis of end-stage renal cancer were eligible for inclusion in this study. Both patients were 39-year-old men. Disease duration ranged from 1 to 3 years, with estimated survival ranging from less than 2 to 6 months. The patients had widespread metastatic disease to lymph nodes, lung, brain, bone, and the contralateral kidney. The pathological diagnosis for these patients was renal cell carcinoma. Prior treatment included surgery, three types of radiation therapy, and targeted...

Claims

1. A composition for treating metastatic cancer and / or terminal cancer in a subject, comprising one or more antineoplastons, wherein the metastatic cancer and / or terminal cancer is characterized by one or more genomic abnormalities in one or more cancer-related genes; the one or more antineoplastons include A10 and AS2-1; A10 contains monosodium phenylacetylglutamate (PG) and monosodium phenylacetylglutamate (iso-PG) in a 4:1 ratio; AS2-1 contains phenylacetate (PN) and monosodium phenylacetylglutamate (PG) in a 4:1 ratio; the metastatic and / or terminal cancer is breast cancer, colorectal cancer, head and neck cancer, kidney cancer, lung cancer, ovarian cancer, pancreatic cancer, or prostate cancer; the one or more cancer-associated genes comprise AKT1, AKT2, ALK, APC, AR, ARAF, ARID1A, BRACA1, BRACA2, BRAF, CCND1, CCNE1, CDK4, CDK6, CDKN2A, CDKN2A / B, CTNNB1, EGFR, EWSR1, FBXW7, FGFR, FLI1, GATA3, GNAQ, KRAS, MAP2K1, MAP2K4, MAP3K1, MET, MYC, NF1, NTRK1, PDGFRA, PIK3CA, PTEN, RAF1, RB1, SDKN2A, SMAD, SMAD4, TERT, or TP53; composition.

2. A composition comprising one or more antineoplastons according to claim 1, wherein the dose of A10 comprises from about 0.4 g / kg / day to about 16 g / kg / day of sodium phenylacetylglutamate (PG) and from about 0.1 g / kg / day to about 4 g / kg / day of sodium phenylacetylisoglutamate (iso-PG).

3. A composition comprising one or more antineoplastons according to claim 1, wherein the dose of AS2-1 comprises from about 0.064 g / kg / day to about 0.48 g / kg / day of phenylacetate (PN) and from about 0.016 g / kg / day to about 0.12 g / kg / day of phenylacetylglutamate (PG).

4. A composition comprising one or more antineoplastons described in claim 1, wherein the one or more genomic abnormalities include mutations, insertions, deletions, chromosomal rearrangements, copy number abnormalities, or any combination thereof.

5. 10. A composition comprising one or more antineoplastons according to claim 1, wherein the subject receives one or more additional therapeutic agents.

6. 6. The composition comprising one or more antineoplastons of claim 5, wherein the one or more additional therapeutic agents comprise a chemotherapeutic agent, a monoclonal antibody, a small molecule, or any combination thereof.

7. 6. The composition comprising one or more antineoplastons of claim 5, wherein the additional therapeutic agent comprises bevacizumab, pazopanib, sorafenib, dasatinib, everolimus, or any combination thereof.

8. 7. The composition comprising one or more antineoplastons of claim 6, wherein the monoclonal antibody comprises adotrastuzumab, alemtuzumab, atezolizumab, avelumab, bevacizumab, blinatumomab, brentuximab, cemiplimab, cetuximab, daratumumab, denosumab, dinutuximab, durvalumab, elotuzumab, gemtuzumab, ibritumomab, inotuzumab, ipilimumab, necitumumab, nivolumab, obinutuzumab, ofatumumab, olaratumumab, panitumumab, pembrolizumab, pertuzumab, ramucirumab, rituximab, tositumomab, trastuzumab, or any combination.

9. Small molecules include abemaciclib, afatinib, alectinib, alpelisib, axitinib, binimetinib, bosutinib, brigatinib, cabozantinib, carfilzomib, ceritinib, gilteritinib, cobimetinib, copanlisib, crizotinib, dabrafenib, dacomitinib, dasatinib, duvelisib, encorafenib, entrectinib, erdafitinib, erlotinib, gefitinib, ibrutinib, imatinib, ivosidenib, and 7. A composition comprising one or more antineoplastons of claim 6, comprising lapatinib, larotrectinib, lenvatinib, lorlatinib, marizomib, neratinib, nilotinib, niraparib, olaparib, osimertinib, palbociclib, pazopanib, ponatinib, regorafenib, ribociclib, rucaparib, sorafenib, sunitinib, talazoparib, trametinib, vandetanib, vemurafenib, or any combination thereof.

10. The composition comprises: increasing the subject's chances of survival; Increases the length of time before transition reducing the likelihood of surgical intervention, reducing the need to administer one or more additional therapeutic agents or regimens; reducing the size of one or more tumors in said subject; Eliminate one or more tumors in said subject. reducing or eliminating the prevalence of one or more genomic abnormalities; restoring normal metabolism of one or more organ systems in said subject; restore one or more aspects of cellular homeostasis and / or cellular functionality, and / or metabolic dysregulation, or A composition comprising one or more antineoplastons according to claim 1, which provides any combination thereof.

11. A composition comprising one or more antineoplastons according to claim 1, wherein the metastatic cancer and / or terminal cancer is breast cancer, and the one or more cancer-related genes include AKT1, APC, AR1DIA, ARAF, BRACA1, BRACA2, CCND1, CCNE1, CDK4, CDK6, CDKN2A, CTNNB1, EGFR, FGFR, GATA3, MAP2K1, MAP2K4, MAP3K1, MET, MYC, NF1, P1K3CA, PDGFRA, PTEN, RAF1, RB1, TP53, or any combination thereof.

12. A composition comprising one or more antineoplastons according to claim 1, wherein the metastatic cancer and / or terminal cancer is colorectal cancer, and the one or more cancer-related genes include APC, ARID1A, BRAF, EGFR, KRAS, P1K3CA, PTEN, SMAD4, TP53, or any combination thereof.

13. A composition comprising one or more antineoplastons described in claim 1, wherein the metastatic cancer and / or terminal cancer is head and neck cancer, and the one or more cancer-related genes include ARID1A, GATA3, GNAQ, or any combination thereof.

14. A composition comprising one or more antineoplastons described in claim 1, wherein the metastatic cancer and / or terminal cancer is renal cancer, and the one or more cancer-related genes include AKT2, CDKN2A / B, PTEN, SDKN2A, or any combination thereof.

15. A composition comprising one or more antineoplastons described in claim 1, wherein the metastatic cancer and / or terminal cancer is lung cancer, and the one or more cancer-related genes include EGFR, EWSR1, FBXW7, FLI1, NF1, SMAD4, TERT, TP53, or any combination thereof.

16. A composition comprising one or more antineoplastons described in claim 1, wherein the metastatic cancer and / or terminal cancer is ovarian cancer, and the one or more cancer-related genes include ALK, AR, ARID1A, BRAF, CCND1, MYC, NF1, NTRK1, PIK3CA, RAF1, SMAD4, TP53, or any combination thereof.

17. A composition comprising one or more antineoplastons described in claim 1, wherein the metastatic cancer and / or terminal cancer is prostate cancer, and the one or more cancer-related genes include APC, CCNE1, EGFR, MYC, NF1, PIK3CA, PTEN, SMAD, TP53, or any combination thereof.

18. A combination for treating metastatic cancer and / or terminal cancer in a subject, comprising A10 and AS2-1, wherein the metastatic cancer and / or terminal cancer is characterized by one or more genomic abnormalities in one or more cancer-associated genes; A10 contains monosodium phenylacetylglutamate (PG) and monosodium phenylacetylglutamate (iso-PG) in a 4:1 ratio; AS2-1 contains phenylacetate (PN) and monosodium phenylacetylglutamate (PG) in a 4:1 ratio; the metastatic and / or terminal cancer is breast cancer, colorectal cancer, head and neck cancer, kidney cancer, lung cancer, ovarian cancer, pancreatic cancer, or prostate cancer; the one or more cancer-associated genes comprise AKT1, AKT2, ALK, APC, AR, ARAF, ARID1A, BRACA1, BRACA2, BRAF, CCND1, CCNE1, CDK4, CDK6, CDKN2A, CDKN2A / B, CTNNB1, EGFR, EWSR1, FBXW7, FGFR, FLI1, GATA3, GNAQ, KRAS, MAP2K1, MAP2K4, MAP3K1, MET, MYC, NF1, NTRK1, PDGFRA, PIK3CA, PTEN, RAF1, RB1, SDKN2A, SMAD, SMAD4, TERT, or TP53; Combination.

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