72 results about "Castration Resistance" patented technology

The present invention provides methods, compositions, and combinations for treating cancer via combined use of a compound of formula (I), and / or their subgenra, or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R1, R2, R3, R8, R9, R11a, R11b, R11c, and R11d are as defined herein, and at least one therapeutically active agents selected from inhibitors of PI3K / AKT / mTOR pathway, active agents associated with the treatment of prostate cancer, and anticancer agents.

Substituted phenylcarbamoyl alkylamino arenes; substituted phenylthiocarbamyl alkylamino arenes; substituted phenylcarbamoyl alkylamino heteroarenes; substituted phenylthiocarbamyl alkylamino heteroarenes; N-substituted aryl, N′-substituted aryl urea compounds; N-substituted aryl, N′-substituted heteroaryl urea compounds; N-substituted aryl, N′-substituted aryl thiourea compounds and N-substituted aryl, N′-substituted heteroaryl thiourea compounds are provided and may find use as androgen receptor modulators. The compounds may find particular use in treating prostate cancer, including castration-resistant prostate cancer and / or hormone-sensitive prostate cancer.

The present invention relates to methods for reducing testosterone levels in a male subject and methods of treating, suppressing, reducing the incidence, reducing the severity, or inhibiting prostate cancer, advanced prostate cancer, castration resistant prostate cancer (CRPC), metastatic castration resistant prostate cancer (mCRPC), and methods of reducing high or increasing PSA levels and / or increasing SHBG levels in a subject suffering from prostate cancer, advanced prostate cancer, castration resistant prostate cancer (CRPC) and metastatic castration resistant prostate cancer (mCRPC). The compounds of this invention suppress free or total testosterone levels despite castrate levels secondary to ADT and reduce high or increasing PSA levels. This reduction in testosterone levels may be used to treat prostate cancer, advanced prostate cancer, CRPC and mCRPC without causing bone loss, decreased bone mineral density, increased risk of bone fractures, increased body fat, hot flashes and / or gynecomastia.

The invention discloses a circRNA relevant to prostatic cancers and application of the circRNA. The circRNA is hsa_circ_0092339. According to the circRNA relevant to prostatic cancers and the application of the circRNA, it is found for the first time that the expression of the hsa_circ_0092339 in castration-resistant prostate cancers is up-regulated, and by detecting the level of the hsa_circ_0092339, whether a testee suffers from castration-resistant prostate cancers or not can be judged.

The present invention relates to methods for reducing testosterone levels by reduction of luteinizing hormone (LH) or independent of LH levels in a male subject and methods of treating, suppressing, reducing the incidence, reducing the severity, or inhibiting prostate cancer, advanced prostate cancer, castration resistant prostate cancer (CRPC), metastatic castration resistant prostate cancer (mCRPC) and palliative treatment of prostate cancer, advanced prostate cancer, castration resistant prostate cancer (CRPC) and metastatic castration resistant prostate cancer (mCRPC), and methods of reducing high or increasing PSA levels and / or increasing SHBG levels in a subject suffering from prostate cancer, advanced prostate cancer, castration resistant prostate cancer (CRPC) and metastatic castration resistant prostate cancer (mCRPC). The compounds of this invention suppress free or total testosterone levels despite castrate levels secondary to ADT and reduce high or increasing PSA levels. This reduction in testosterone levels may be used to treat prostate cancer, advanced prostate cancer, CRPC and mCRPC without causing bone loss, decreased bone mineral density, increased risk of bone fractures, increased body fat, hot flashes and / or gynecomastia.

The invention discloses application of neurotensin in diagnosis on castration resistant prostate cancer neuroendocrine subtype and prognosis judgment. The neurotensin level in serum of a subject is detected, correlation analysis is performed on the neurotensin level and clinical data of the subject, and meanwhile a basic biological experimental verification is utilized to prove that the neurotensin and the castration resistant prostate cancer neuroendocrine subtype have large correlation. By means of the application, a novel method is provided for clinic diagnosis on the castration resistant prostate cancer neuroendocrine subtype and the prognosis judgment.

Methods of the present disclosure provide for detection of mutations and splice variants of the androgen receptor using a non-invasive approach, RNAseq, for examining circulating tumor cells.

The present application relates to treating and / or preventing prostate cancer, including metastatic and / or castrate-resistant prostate cancer, in a subject in need of treatment, comprising administering a compound of Formula (I),or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate, polymorph, isotopic derivative, or prodrug thereof, wherein R1, R2, R3, X1, X2, X3, X4 and n are defined herein.

The present disclosure relates to combination treatments with anti-androgen therapeutics, including enzalutamide, and prostate-specific membrane antigen (PSMA)-binding polypeptides including multi-specific polypeptide therapeutics that specifically target cells expressing PSMA and are capable of redirecting T-cell cytotoxicity. Such therapeutics are useful for the treatment of prostate cancer (e.g., castration-resistant prostate cancer). In one embodiment, multi-specific polypeptide therapeutics bind both PSMA-expressing cells and the T-cell receptor complex on T-cells to induce target-dependent T-cell cytotoxicity, activation, and proliferation. The disclosure also provides compositions comprising the multi-specific polypeptide therapeutics and one or more anti-androgen therapeutics.

The invention provides a targeted prodrug for treating targeted prodrug for treating castration-resistant prostate cancer; the targeted prodrug is P (OEGMA-co-CPT-co-AR16), wherein POEGMA is a water-soluble polymer having a long circulation function, CPT is chemotherapeutic camptothecin having an antineoplastic activity and AR16 is polypeptide showing specific targeting to castration-resistant prostate cancer; the invention also provides a method for preparing the P (OEGMA-co-CPT-co-AR16), wherein the method, on the basis of a polymer P (OEGMA-co-BSMA) containing -thiocarboxyl, carries out esterification and ammonolysis reactions so as to modify CPT and AR16 on the polymer in a covalent mode, so that the targeted CPT macromolecular prodrug P (OEGMA-co-CPT-co-AR16) is obtained. In addition, the invention also provides a nano preparation and a preparation method of the targeted prodrug. The nano preparation of the targeted prodrug P (OEGMA-co-CPT-co-AR16) prepared by the method disclosed by the invention can be used for effectively killing cancer cells with a relatively low dosage, and can show an excellent specific recognition effect on castration-resistant prostate cancer.

The invention relates to a modified LNA oligonucleotide for targeting lncRNAs to resist AR-related tumor castration-recurrent. Researches show that the expression of PCGEM1 is highly correlated with malignancy as well as recurrence and metastasis of prostate cancers, and is highly positive correlated with the expression of an AR isoform, such as AR3 (AR-V7), and researches also prove that the PCGEM1 modifies and regulates the expression of the AR isoform, such as AR3, through alternative transcription. Based on the research results, the LNA oligonucleotide can directly target the target gene PCGEM1, can efficiently and accurately block the expression of the PCGEM1, and blocks a PCGEM1-mediated androgen receptor isoform AR3 through joint targeting, so that the castration resistance as well as recurrence and metastasis possibility of AR-related tumors subjected to hormone castration treatment can be effectively reduced. The modified LNA oligonucleotide is good in specificity and high in stability; animal experiments show that the modified LNA oligonucleotide can suppress tumor growth, and the effect is very significant.

The present application relates to treating and / or preventing prostate cancer, including metastatic and / or castrate-resistant prostate cancer, in a subject in need of treatment having particular somatic AR tumor biomarker status, comprising administering a compound of Formula (I),or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate, polymorph, isotopic derivative, or prodrug thereof, wherein R1, R2, R3, X1, X2, X3, X4, and n are defined herein.

Provided herein are methods useful for identifying compounds that modulate the activity of an androgen receptor, or variant thereof. In particular, this invention encompasses reagents and strategies for identifying compounds that target specific androgen receptor splice variants, for example, AR-v7, that are important for prostate cancer progression and metastasis, for example in the development of castration-resistant prostate cancer. Also provided herein are specific compounds that modulate the activity of an androgen receptor, or variant thereof, pharmaceutical compositions, and methods of using these compounds and pharmaceutical compositions for modulating the activity of an androgen receptor, or variant thereof in vitro and in vivo.

The present invention relates to methods for reducing testosterone levels in a male subject and methods of treating, suppressing, reducing the incidence, reducing the severity, or inhibiting prostate cancer, advanced prostate cancer, castration resistant prostate cancer (CRPC), metastatic castration resistant prostate cancer (mCRPC), and methods of reducing high or increasing PSA levels and / or increasing SHBG levels in a subject suffering from prostate cancer, advanced prostate cancer, castration resistant prostate cancer (CRPC) and metastatic castration resistant prostate cancer (mCRPC). The compounds of this invention suppress free or total testosterone levels despite castrate levels secondary to ADT and reduce high or increasing PSA levels. This reduction in testosterone levels may be used to treat prostate cancer, advanced prostate cancer, CRPC and mCRPC without causing bone loss, decreased bone mineral density, increased risk of bone fractures, increased body fat, hot flashes and / or gynecomastia.

The present application relates to treating and / or preventing prostate cancer, including metastatic and / or castrate-resistant prostate cancer, in a subject in need of treatment, comprising administering a compound of Formula (I),or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate, polymorph, isotopic derivative, or prodrug thereof, wherein R1, R2, R3, X1, X2, X3, X4, and n are defined herein.

The invention discloses a circRNA relevant to prostatic cancers and application of the circRNA. The circRNA is hsa_circ_0092339. According to the circRNA relevant to prostatic cancers and the application of the circRNA, it is found for the first time that the expression of the hsa_circ_0092339 in castration-resistant prostate cancers is up-regulated, and by detecting the level of the hsa_circ_0092339, whether a testee suffers from castration-resistant prostate cancers or not can be judged.

The invention relates to a tumor targeted diagnosis and treatment integrated drug compound, in particular to an <18 / 19>F-labeled PSMA targeted diagnosis and treatment integrated small molecular drug conjugate, a preparation method and an application of the <18 / 19>F-labeled PSMA targeted diagnosis and treatment integrated small molecular drug conjugate. By utilizing a PSMA targeted small molecular ligand, a DM1 drug with a high toxicity killing effect is delivered to PSMA positive prostate cancer cells in a targeted manner, the effect of effectively killing castration-resistant prostate CRPC cells with relative drug resistance is expected to be achieved, besides, the toxic and side effects of the DM1 on the whole body are effectively controlled and reduced, and the tolerance of a patient is improved; and besides, on the basis, a tumor diagnosis and treatment integrated mode is introduced, molecular imaging diagnosis is used for assisting in visualizing the in-vivo transfer process of drugs, predicting the curative effect of the patient, knowing the in-vivo distribution of the drugs, achieving real-time monitoring and individualized administration of the tumor treatment effect and achieving diagnosis and treatment integration.

The invention belongs to the technical field of biological medicines, relates to an application of PRPF6 to treatment of prostatecancer and castration-resistant prostate cancer, and provides an application of a PRPF6 targeting inhibitor to preparation of drugs and medical compositions for preventing or treating prostate cancer and castration-resistant prostate cancer. It is found for the first time that PRPF6 can promote the progress of the prostate cancer and the castration resistance to prostate cancer, the PRPF6 is higher in expression in prostate cancer tissue with higher grade malignancy,and inhibition of the PRPF6 has the effect of obviously inhibiting occurrence and development of prostate cancer and castration-resistant prostate cancer. The invention relates to application of thePRPF6 to treatment and resisting of the prostatecancer and the castration-resistant prostate cancer. It is found that the PRPF6 has a potential drug resistance function in the prostatecancer and castration-resistant prostate cancer endocrine drugs, a PRPF6 micromolecule inhibitor and siRNA are prepared, or it is found that PRPF6 transcription is inhibited to generate miRNA so as to treat clinicalprostatecancer and castration-resistant prostate cancer. The invention provides a new thought and new target point for treating prostaticcancer and castration-resistant prostatic cancer.

The invention discloses an antisense oligonucleotide of METTL3 and an application of the antisense oligonucleotide in prostatic cancer. By inhibiting the expression level of METTL3, proliferation of castration-resistant prostate cancer cells can be reduced, the drug sensitivity of drug-resistant prostate cancer cell strains can be recovered, and a new means is provided for treating castration-resistant prostate cancer and drug-resistant prostate cancer.

The invention discloses application of stachyose in preparation of a medicine for treating castration-resistant prostate cancer, and belongs to the technical field of biological medicine. The application of stachyose provides a new strategy for preparing the medicine for treating the CRPC by combining the stachyose with an androgen receptor antagonist for the first time, and multi-angle and multi-level verification research is carried out. A stachyose and androgen receptor combined pharmaceutical composition can be used for treating the castration-resistant prostate cancer, the effect of enzalutamide on inhibiting the castration-resistant prostate cancer is remarkably improved, a natural compound is applied to the advanced stage of the cancer, and the pharmaceutical composition has important clinical treatment significance.

The invention belongs to the field of prognosis evaluation of metastatic castration-resistant prostate cancer patients, and particularly relates to a prognosis prediction model of metastatic castration-resistant prostate cancer patients in abiraterone treatment and an establishment method and application of the prognosis prediction model. For mCRPC patients receiving abiraterone first-line treatment, scoring can be conducted through the column diagram, the prediction probability that PSA progress does not happen to the patients in the sixth month and the twelfth month and the PSA progress time does not exist in the middle position are obtained according to the corresponding positions of the total branch column diagram, and therefore use of clinicians in daily work is more convenient.

The invention relates to an in-vitro mini-reporter gene used for predicating androgen receptor posttranscriptional modification sites and an application thereof. Experiments indicate that lncRNA PCGEM1 directly decides castration resistance or recurrence and metastasis of hormones for expressing the tumours of an androgen receptor after castration by regulating the posttranscriptional modification of the isomer AR-V7(AR3) pre-mRNA of the androgen receptor; on this basis, sequences containing exons Exon3 and Exon4 of the pre-mRNA of the AR are selected to construct the mini-reporter gene through gene cloning; on one hand, the mini-reporter gene is used for predicating high-risk factors causing the hormone castration recurrence and metastasis of the tumours related to the androgen receptor, such as prostatic cancer; on the other hand, the expression and action of the specific target gene sites can be intuitively, efficiently and accurately verified and blocked through the mini-reporter gene.

It is disclosed herein methods of treating prostate cancer comprising administering to the subject the combination of androgen deprivation therapy (ADT) and a vaccine directed against the androgen receptor or a fragment of the androgen receptor. Also disclosed are methods of increasing the efficacy of androgen deprivation therapy in a subject with prostate cancer comprising administering to the subject an effective amount of a vaccine against the androgen receptor or fragments thereof wherein the method inhibits, delays or reduces the growth of the prostate cancer and / or the development of castration-resistant prostate cancer.

The invention provides methods for treating prostate cancer, including metastatic castration-resistant prostate cancer, comprising administering to a subject in need thereof a BET faromadomain inhibitor in combination with a second agent.

The invention includes 2-β-naphthyl-acetic acid derivatives, which are selective AKR1C3 inhibitors. In certain embodiments, the compounds of the invention are (R)-naproxen analogs. The invention further includes methods of treating cancer, such as prostate cancer and / or castration-resistant prostate cancer, using at least one compound of the invention.

This invention is directed to the treatment of cancer, particularly castration- resistant prostate cancer and osteoblastic bone metastases, with a dual inhibitor of MET and VEGF.

Disclosed herein are novel biomarkers for detecting resistance and sensitivity to abiraterone acetate-glucocorticoid treatment in a patient having metastatic castration resistant prostate cancer. Alsoprovided are methods of diagnosing and treating abiraterone acetate-glucocorticoid resistant and abiraterone acetate-glucocorticoid sensitive metastatic castration resistant prostate cancer.