Tumor treatment medication auxiliary system and pharmaceutical composition

Abstract

The invention discloses a medication auxiliary system for tumor treatment and a pharmaceutical composition. The tumor treatment medication auxiliary system provided by the embodiment of the invention comprises a marker acquisition module used for acquiring a tumor marker of a patient; the medication suggestion module is used for giving corresponding medication suggestions based on the obtained tumor markers; the medication suggestion comprises the following steps: if the tumor marker contains BRAF V600E mutation, TERT promoter mutation and SNP rs2853669TT, recommending an inhibitor which is sensitive to a tumor carrying a triple gene combination of the BRAF V600E mutation, the TERT promoter mutation and the SNP rs2853669TT; the inhibitors comprise a BRAF inhibitor, an MEK inhibitor, an MYC inhibitor, an RAS inhibitor and a PI3K / AKT inhibitor. Expression of BRAF, MEK, MYC, RAS, PI3K / AKT and the like is specifically inhibited, and wide killing on normal cells is avoided. The high specificity improves the selectivity and safety of treatment, and reduces the side effects caused by traditional chemotherapy and radiotherapy.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological medicine, in particular to a drug assisting system for tumor treatment and a pharmaceutical composition. BACKGROUND

[0002] Current targeted therapy for cancer mainly focuses on single gene mutation or signal pathway, for example, BRAF inhibitor is used for treating melanoma carrying BRAF V600E mutation. However, for cancer patients carrying triple gene combination of BRAF V600E, TERT promoter mutation and SNP rs2853669TT, there is a lack of effective drug recommendation. SUMMARY

[0003] The technical problem to be solved by the present application is that there is a lack of effective drug recommendation for cancer patients carrying triple gene combination of BRAF V600E, TERT promoter mutation and SNP rs2853669TT. In order to solve the technical problem, the present application provides a drug assisting system. The system is based on tumor markers, and inhibits key molecular steps in related signal pathways by precisely targeting tumor cells with the highest malignancy carrying specific gene combination (BRAF V600E, TERT promoter mutation and SNP rs2853669TT), so as to improve the therapeutic effect and improve the prognosis of patients. The inhibitor provided by the embodiment of the present application shows significant therapeutic effect in the carrying cell line. On the contrary, if the three genotypes do not exist, the expected effect will be poor, and such patients should avoid using these drugs to avoid side effects.

[0004] In a first aspect, the present application provides a drug assisting system for tumor treatment, comprising:

[0005] a marker acquisition module, configured to acquire tumor markers of a patient;

[0006] a drug recommendation module, configured to give corresponding drug recommendation based on the acquired tumor markers; the drug recommendation comprises: if the tumor markers contain BRAF V600E mutation, TERT promoter mutation and SNP rs2853669TT, recommending an inhibitor sensitive to tumor carrying triple gene combination of BRAF V600E mutation, TERT promoter mutation and SNP rs2853669TT.

[0007] The inhibitor includes: BRAF inhibitor, MEK inhibitor, MYC inhibitor, RAS inhibitor and PI3K / AKT inhibitor.

[0008] The following are preferred technical solutions of the present application, but are not intended to limit the technical solutions provided by the present application. Through the following preferred technical solutions, the purposes and beneficial effects of the present application can be better achieved and implemented.

[0009] As a preferred technical solution, the tumor medication auxiliary system, wherein the medication recommendation further comprises: if the tumor marker does not contain BRAF V600E mutation, TERT promoter mutation and SNP rs2853669TT, the inhibitor is not recommended.

[0010] As a preferred technical solution, the BRAF inhibitor includes but is not limited to: GSK2118436A (Dabrafenib), PLX4032 / RG7204 / RO5185426 (Vemurafenib), CEP-32496 / RXDX-105 (Agerafenib), RO5126766 / CH5126766 / VS 6766 / CKI-27 / R-7304 / RG-7304 (Avutometinib), BGB-283 (Lifirafenib), LXH254 (Naporafenib), HM95573 (Belvarafenib), RAF / KIN_2787 (Exarafenib), LGX818 (Encorafenib), PF-07284890 (Tinlorafenib), PLX8394 / FORE8394 (Plixorafenib), Everafenib, Uplarafenib, PF-04880594, PF-07799933, PLX7922, PLX-4720, PLX7904, AZ628, AZ304, RAF709, TBAP-001, CCT196969, CCT241161, TAK632, LY3009120 (DP-4978), BI-882370, GDC-0879, L-779450, HG6-64-1, Vem-L-Cy5, LUT014, ARQ-736, BGB-3245, SB-590885, SHR902275, GNE-9815, AD57, AD80, NST-628, KG5, ML786 dihydrochloride, Takeda-6D, Rafoxanide;MEK inhibitors include, but are not limited to, AZD6244 (Selumetinib), HL-085 (Tunlametinib), RDEA119 (Refametinib), AS703026 (Pimasertib), PD0325901 (Mirdametinib), GSK1120212 (Trametinib), MEK162 (Binimetinib), GDC-0973 (Cobimetinib), PD0184264 / ATR-002, (Zapnometinib), WX-554, AZD-8330, GDC-0623, CI-1040, TAK733, SL-327, U0126, PD318088, BIX 02188, BIX 02189, PD98059, PD184161, PD184352 (CI-1040), E-6201, SHR 7390, RO4987655, REC-4881, PF-07799544, NFX-179, FCN-150, GW284543 (unc10225170), CS3006, IMM-1-104, BI 3011441, Myricetin, EKB-569 (Pelitinib), APS-2-79, BI-847325, RO-5126766, AS-703988, CH5126766 (Avutometinib);The MYC inhibitors include, but are not limited to: MYC degrader 1, MYC-IN-2, MYC-IN-3, MYC-RIBOTAC, Mycro 1, Mycro 2, Mycro 3, MYCMI-6, MYCi 361, MYCi 975, c-MYC inhibitor 4, c-MYC inhibitor 5, c-MYC inhibitor 6, c-MYC inhibitor 8, c-MYC inhibitor 9, c-MYC inhibitor 10, c-MYC inhibitor 11, c-MYC inhibitor 12, c-MYC inhibitor 13, c-MYC inhibitor 14, c-MYC inhibitor 15, PROTAC c-Myc degrader-1, NTB2R, MYRA-A, DBPR728, MDEG-541, EN4, MY05, 10058-F4, RA-V, NSC308848, rel-AZ5576, NY2267, JY-3-094, TS-2, sAJM589, VPC-70619, WBC100, 6K465, KSI-3716, IZTZ-1, VPC-70063, KJ Pyr 9, Stauprimide, 10074-A4, EP-12, hnRNPK-IN-1, IRES-C11, IZCZ-3, 10074-G5, ML327, m-Se3, C SI86, Antiproliferative agent-64, Lusianthridin, CT113, Anticancer agent 84, PPA24, THZ1 Hydrochloride, THZ1, BAY1238097, AZD5153, CotyleninA, NSC10010 hydrochloride, SYUIQ5, Ro 31-7837, APTO-253 hydrochloride, APTO-253, Anticancer agent 263, g-Sitosterol, A62176 hydrochloride, and OMO-103;The RAS-related inhibitors include, but are not limited to: Sotorasib (AMG 510), Adagrasib (MRTX849) Statins, GDC-6036, JDQ443, TNO155, LY3537982, MRTX1133 (Mirati), ASP3082, BI 1701963, TNO155, RLY-1971, Ulixertinib, Binimetinib, Tipifarnib, KRASG12C-PROTAC (such as LC-2), RMC-6236; and the PI3K / AKT inhibitors include, but are not limited to: Buparlisib (BKM120), Pilaralisib (SAR245408), Copanlisib (BAY 80-6946), ZSTK474, Alpelisib (BYL719), Inavolisib (GDC-0077), GSK2636771, Idelalisib, Duvelisib, Eganelisib (IPI-549), Dactolisib (BEZ235), Voxtalisib (SAR245409), Capivasertib (AZD5363), Ipatasertib (GDC-0068), Miransertib (ARQ 092), Borussertib (ARQ 751), Everolimus, Sirolimus, Temsirolimus, Ridaforolimus, Sapanisertib (TAK-228), Vistusertib (AZD2014), AKT-PROTAC (MS21), CUDC-907, liposome-encapsulated PI3K inhibitors, and the like.

[0011] As a preferred technical solution, the specific inhibitor, wherein the tumor carrying the triple gene combination of BRAF V600E mutation, TERT promoter mutation and SNP rs2853669TT includes: thyroid cancer, melanoma, lung cancer, breast cancer, gastrointestinal tumor and urinary system tumor.

[0012] As a preferred technical solution, the BRAF, MEK, MYC, RAS, PI3K / AKT inhibitor, wherein the thyroid cancer includes: thyroid papillary carcinoma, thyroid follicular carcinoma, and thyroid anaplastic carcinoma.

[0013] As a preferred technical solution, the tumor drug adjuvant system, wherein the lung cancer includes: non-small cell lung cancer, lung adenocarcinoma, and small cell lung cancer.

[0014] The second aspect is a pharmaceutical composition, wherein the pharmaceutical composition comprises the BRAF, MEK, MYC, RAS, PI3K / AKT inhibitor described above.

[0015] The third aspect is an application of the pharmaceutical composition of the second aspect in the preparation of a drug for treating tumors carrying a triple genetic combination of BRAF V600E mutation, TERT promoter mutation and SNP rs2853669TT.

[0016] As a preferred technical solution, the application, wherein the tumors carrying a triple genetic combination of BRAF V600E mutation, TERT promoter mutation and SNP rs2853669TT include thyroid cancer, melanoma, lung cancer, breast cancer, gastrointestinal tumors and urinary system tumors.

[0017] The fourth aspect is a method for eliminating tumor cells carrying a triple genetic combination of BRAF V600E mutation, TERT promoter mutation and SNP rs2853669TT for non-therapeutic purposes, wherein the pharmaceutical composition described above is contacted with the tumor cells.

[0018] Compared with the prior art, the embodiments of the present application have the following advantages:

[0019] According to the tumor treatment drug auxiliary system provided by the embodiment of the present application, the corresponding inhibitor can be given according to the obtained target tumor marker, and the expression of BRAF, MEK, MYC, RAS, PI3K / AKT, etc. is inhibited, thereby avoiding the extensive killing of normal cells. This high specificity improves the selectivity and safety of treatment, and reduces the side effects brought by traditional chemotherapy and radiotherapy. BRIEF DESCRIPTION OF DRAWINGS

[0020] In order to more clearly illustrate the technical solutions in the embodiments of the present application or the prior art, the drawings needed in the embodiment or prior art description will be briefly introduced below. Obviously, the drawings in the following description are only some embodiments described in the present application, and those skilled in the art can obtain other drawings according to these drawings without creative labor.

[0021] Figure 1The role of SNP rs2853669 in the expression regulation of TERT provided by the embodiment of the present application; the expression amount of TERT in a tumor cell line simultaneously carrying BRAF V600E, TERT promoter mutation and SNP rs2853669TT is much higher than that in a cell line with other genetic backgrounds, and the parent cell naturally carrying rs2853669TT genotype is edited and converted into rs2853669CC by using CRISPR / Cas9 technology, so that the expression amount of TERT is significantly reduced.

[0022] Figure 2 The importance of three transcription factors GABPA, MYC and ETS2 in the expression regulation of mutant TERT provided by the embodiment of the present application, and there is a physical interaction between the three transcription factors GABPA, MYC and ETS2.

[0023] Figure 3 The embodiment of the present application provides that in a tumor cell line simultaneously carrying BRAF V600E, TERT promoter mutation and SNP rs2853669TT, BRAF V600E regulates the expression of mutant TERT by regulating the DNA binding force of GABPA, MYC and ETS2 in the TERT promoter region.

[0024] Figure 4 The embodiment of the present application provides that BRAF V600E regulates the expression of GABPB, MYC and ETS2 through the MAP kinase pathway.

[0025] Figure 5 The embodiment of the present application provides a complex model of GABPA, MYC and ETS2 predicted by AlphaFold3 through physical interaction.

[0026] Figure 6 The embodiment of the present application provides that the expression regulation of MYC on TERT does not depend on the traditional dimerization with MAX to play a role.

[0027] Figure 7 The embodiment of the present application provides that targeting degradation of MYC causes severe apoptosis in a tumor cell line simultaneously carrying BRAF V600E, TERT promoter mutation and SNP rs2853669TT compared with other genotype cell lines.

[0028] Figure 8 The specific molecular mechanism of the present application is shown in the schematic diagram.

[0029] Figure 9 The tumor treatment drug auxiliary system provided by the embodiment of the present application is shown in the schematic diagram. DETAILED DESCRIPTION

[0030] In the following, the technical solutions in the embodiments of the present application will be described clearly and completely in combination with the drawings in the embodiments of the present application, so that those skilled in the art can better understand the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative work fall within the protection scope of the present application.

[0031] Telomerase reverse transcriptase (TERT) has been widely recognized as a strong oncogenic factor independent of telomerase function, which can directly promote the proliferation, invasion, anti-apoptosis, angiogenesis and metastasis of cancer cells and other malignant biological behaviors. TERT gene is usually in a silent state in somatic cells, but is reactivated in human cancers. Since the reactivation mutations in the TERT promoter were found to be closely related to tumorigenesis in melanoma, the oncogenic status of TERT has been established. Currently, such mutations have been confirmed to be significantly related to tumor progression and invasiveness in a variety of malignant tumors. The most common TERT promoter mutations, Chr. 5: 1,295,228 C>T (TERT C228T) and Chr. 5: 1,295,250 C>T (TERT C250T) located in the core promoter region of TERT (124 bp and 146 bp upstream of the translation start site TSS, respectively), activate TERT expression by creating ETS family transcription factor (such as GABPA / GABPB complex) binding sites.

[0032] The single nucleotide polymorphism (SNP) rs2853669 located in the ETS2 binding site of the TERT promoter region (245 bp upstream of the TSS) was found to be associated with a variety of cancers. The rs2853669 C>T variation can maintain the normal function of the ETS2 binding site, stabilize the TERT promoter activity; while the rs2853669 T>C variation destroys the binding site, significantly weakens the binding ability of the transcription factor and reduces the TERT activity. Studies have shown that the activating effect of rs2853669 C>T on TERT is significantly enhanced when the TERT promoter mutation is present at the same time, and the co-mutation of rs2853669 TT and TERT C228T / C250T significantly worsens the prognosis of cancer.

[0033] BRAF V600E, as a common oncogenic mutation, can drive tumorigenesis by continuously activating the MAP kinase pathway, and plays a key role in malignant tumors such as melanoma and papillary thyroid carcinoma (PTC). The coexistence of BRAF V600E and TERT promoter mutation is particularly prominent, and the "genetic duet" formed by the two is closely related to the high invasiveness of PTC and melanoma. Molecular mechanism studies have shown that BRAF V600E upregulates GABPB expression through the MAP kinase pathway, promotes the formation of GABPB-GABPA complex, and then specifically binds and activates the mutant TERT promoter, thereby strongly driving TERT expression.

[0034] The genetic triad of BRAF V600E, TERT promoter mutation and rs2853669C>T is significantly related to the most invasive clinical phenotype of PTC, revealing the core role of this unique genetic background in cancer progression. The present application is inspired by the influence of the coexistence of BRAF mutation and TERT promoter mutation and SNP rs2853669TT on the prognosis of PTC patients. Through the exploration of the molecular mechanism of this specific clinical phenomenon, a targeted treatment plan for this situation is determined.

[0035] The present application provides the specific molecular mechanism that the coexistence of BRAF V600E, TERT promoter mutation and rs2853669TT leads to patients with significantly poor survival prognosis, and the present application provides that targeting MYC is the most effective treatment method for this specific gene combination. First, in different tumor cell lines, the expression level of TERT in tumor cell lines simultaneously carrying BRAF V600E, TERT promoter mutation and rs2853669TT is much higher than that of other genotypes (A, Figure 1 B), Figure 1 C), and the use of CRISPR / Cas9 technology to edit the parent cells naturally carrying rs2853669TT genotype into rs2853669CC makes the expression level of TERT significantly decrease (E). Figure 1 Figure 1 Figure 2 A-C). Subsequently, the inventors found that GABPA, MYC and ETS2 form a complex and affect each other's DNA binding force in the TERT promoter region through physical interaction, and this interaction further regulates the expression of mutant TERT (F). Figure 2 ​​The inventors confirmed that in tumor cell lines carrying both BRAF V600E and TERT promoter mutations and SNP rs2853669TT, BRAF V600E regulates the expression of mutant TERT by regulating the DNA binding of GABPA, MYC, and ETS2 in the TERT promoter region ( Figure 3 ), and this result is due to BRAF V600E regulating the expression of GABPB, MYC and ETS2 through the MAP kinase pathway ( Figure 4 The inventors then used AlphaFold3 to predict the complex model formed by physical interactions among GABPA, MYC, and ETS2 ( Figure 5 ). The inventors have also demonstrated that MYC's regulation of TERT expression does not rely on the traditional belief that it forms a dimer with MAX to exert its effect ( Figure 6 Finally, the present invention found that targeted degradation of MYC caused severe apoptosis in tumor cell lines carrying BRAF V600E, TERT promoter mutations and SNPrs2853669TT compared to other genotype cell lines ( Figure 7 ).

[0036] Based on the above findings, the inventors provide a tumor treatment medication auxiliary system, such as Figure 9 As shown, it includes: a marker acquisition module 10 for acquiring a patient's tumor markers; a medication recommendation module 20 for providing corresponding medication recommendations based on the acquired tumor markers; the medication recommendation includes: if the tumor markers include BRAF V600E mutation, TERT promoter mutation, and SNP rs2853669TT, recommending an inhibitor that is sensitive to tumors carrying the triple gene combination of BRAF V600E mutation, TERT promoter mutation, and SNP rs2853669TT. The inhibitor includes but is not limited to the following drugs that can effectively eliminate tumors carrying the BRAF V600E mutation, TERT promoter mutation, and SNP rs2853669TT gene trio:

[0037] MYC degrader 1 (compound A80.2 HC1), MYC-IN-2, MYC-IN-3 (compound 37), MYC-RIBOTAC, Mycro 1, Mycro 2, Mycro 3, MYC MI-6 (NSC 354961), MYC i361 (NUCC-0196361), MYC i975, c-MYC inhibitor 4, c-MYC inhibitor 5 (DA3), c-MYC inhibitor 6 (compound A102), c-MYC inhibitor 8 (compound 56), c-MYC inhibitor 9 (compound 332), c-MYC inhibitor 10 (compound 17), c-MYC inhibitor 11 (compound 67e), c-MYC inhibitor 12 (compound 67h), c-MYC inhibitor 13 (compound A6), c-MYC inhibitor 14 (compound 13A), c-MYC inhibitor 15 (compound A5), PROTAC c-Myc degrader-1 (compound A153), NTB2R, MYRA-A, DBPR728, MDEG-541, EN4, MY05, 10058-F4, RA-V, NSC308848, rel-AZ5576, NY2267, JY-3-094, TS-2, sAJM589, VPC-70619, WBC100, 6K465, KSI-3716, IZTZ-1, VPC-70063, KJ Pyr 9, Stauprimide, 10074-A4, EP-12, hnRNPK-IN-1, IRES-C11, IZCZ-3, 10074-G5, ML327, m-Se3, C SI86,Antiproliferative agent-64 (compound 76), Lusianthridin, CT113, Anticancer agent 84, PPA24, THZ1 Hydrochloride, THZ1, BAY1238097, AZD5153, CotyleninA, NSC10010 hydrochloride, SYUIQ5, Ro 31-7837, APTO-253 hydrochloride, APTO-253 (LOR-253), Anticancer agent 263 (compound 7), γ-Sitosterol, A62176 hydrochloride, OMO-103, etc.

[0038] These inhibitors can specifically act on tumor cells carrying the triple genetic combination of BRAF V600E mutation, TERT promoter mutation and SNP rs2853669TT, significantly promote the severe apoptosis of tumor cells by inhibiting the expression of TERT.

[0039] The MYC inhibitor provided by the present application is suitable for various types of cancers, especially those cancer types that exhibit the triple genetic combination of BRAF V600E mutation, TERT promoter mutation and SNP rs2853669TT, including but not limited to: thyroid cancer: such as thyroid papillary carcinoma, thyroid follicular carcinoma, thyroid poorly differentiated carcinoma, thyroid anaplastic carcinoma, oxyphilic cell thyroid carcinoma, etc. nervous system tumors: such as glioblastoma, astrocytoma, medulloblastoma, neuroblastoma, malignant peripheral nerve sheath tumor, tubular membrane tumor, etc. chest tumors: such as pleural mesothelioma, non-small cell lung cancer, lung adenocarcinoma, small cell lung cancer, etc. head and neck tumors: such as sinus squamous cell carcinoma, oral squamous cell carcinoma, laryngeal squamous cell carcinoma, hypopharyngeal squamous cell carcinoma, adenoid cystic carcinoma, etc. digestive system tumors: such as esophageal cancer, esophagogastric junction cancer, gastrointestinal stromal tumor, gallbladder cancer, biliary tract cancer, hepatocellular carcinoma, appendix goblet cell adenocarcinoma, pancreatic neuroendocrine tumor, intraductal papillary mucinous tumor, duodenal cancer, small intestine cancer, colon cancer, rectal cancer, etc. urinary system tumors: such as renal clear cell carcinoma, unclassified renal cell carcinoma, MiT family translocation renal cell carcinoma, plasmacytic / signed cell bladder cancer, bladder urothelial carcinoma, upper urinary tract urothelial carcinoma, etc. soft tissue tumors: such as solitary fibrous tumor, perivascular cell tumor, liposarcoma, fibrosarcoma, osteosarcoma, leiomyosarcoma, round cell sarcoma, angiosarcoma, undifferentiated pleomorphic sarcoma, malignant fibrous histiocytoma, etc. skin cancer: such as melanoma, basal cell carcinoma, cutaneous squamous cell carcinoma, Merkel cell carcinoma, etc. hematological tumors: such as Hodgkin's lymphoma, mature B cell tumor, mantle cell lymphoma, diffuse large B cell lymphoma, peripheral T cell lymphoma, follicular lymphoma, histiocytic / dendritic cell tumor, splenic marginal zone lymphoma, acute myeloid leukemia, etc.

[0040] The tumor treatment drug auxiliary system provided by the present application ensures that the treatment drug can be selected according to the molecular characteristics of the cancer, thereby improving the accuracy of the treatment drug and helping to improve the prognosis of the patient. This strategy is particularly suitable for cancer types that exhibit the coexistence of BRAF mutation, TERT promoter mutation and SNP rs2853669TT, such as thyroid papillary carcinoma and melanoma.

[0041] Application Example One: Precision Treatment of Thyroid Papillary Carcinoma (PTC) Patients

[0042] Case Background: Patient Wang, 45 years old, female, diagnosed with advanced thyroid papillary carcinoma (PTC). Genetic test results show that the patient carries BRAF V600E mutation, TERT promoter mutation (TERT C228T), and SNP rs2853669TT. The coexistence of these genetic mutations makes the patient's cancer highly invasive and poorly responds to traditional radioactive iodine (RAI) treatment.

[0043] Through next-generation sequencing technology, it is confirmed that the patient carries BRAF V600E mutation, TERT C228T mutation and SNPrs2853669TT.

[0044] MYC degrader1 is recommended for targeted therapy. MYC degrader1 can specifically inhibit the expression of MYC, thereby blocking the tumor cell proliferation signal pathway driven by BRAF V600E and TERT promoter mutation. The treatment regimen includes oral administration of MYC degrader1 once a day for 8 weeks.

[0045] After 8 weeks of treatment, the patient's tumor volume is significantly reduced, and the thyroid function index returns to normal.

[0046] Gene expression analysis shows that the expression level of TERT is significantly decreased, indicating that the MYC inhibitor effectively inhibits the proliferation and survival of tumor cells. The patient's quality of life is significantly improved, and the side effects are controllable. Through the treatment strategy of targeting MYC, the patient Wang's thyroid papillary carcinoma has been effectively controlled. This case demonstrates the potential of the present application in treating cancer patients carrying specific gene combinations, especially those who do not respond well to traditional treatment regimens.

[0047] Application Example Two: Personalized Treatment of Melanoma Patients (Single Drug Therapy Based on Targeting MYC)

[0048] Case Background: Patient Li, 58 years old, male, diagnosed with advanced melanoma. Genetic testing results show that the patient not only carries BRAF V600E mutation, but also has TERT promoter mutation (TERT C250T) and SNPrs2853669TT at the same time. The coexistence of these gene mutations makes the patient's melanoma show high invasiveness and drug resistance, and the effect of traditional treatment regimens is limited.

[0049] Through next-generation sequencing technology, it is confirmed that the patient carries BRAF V600E mutation, TERT C250T mutation and SNPrs2853669TT.

[0050] MYC degrader1 is recommended for single drug therapy. MYC degrader1 can specifically degrade MYC protein, thereby blocking the tumor cell proliferation signal pathway driven by BRAF V600E and TERT promoter mutation. The treatment regimen includes oral administration of MYC degrader1 once a day for 12 weeks.

[0051] Periodic imaging and tumor marker tests are performed to monitor the tumor's response. At the same time, the patient's side effects are closely monitored, and the drug dosage is adjusted as needed. For example, if the patient has mild liver function abnormalities, the dosage of MYC degrader 1 can be appropriately reduced, and liver protection treatment can be given.

[0052] Through gene expression analysis, the expression levels of TERT and other key genes are monitored to evaluate the treatment effect. After 4 weeks of treatment, the expression level of TERT is significantly reduced, indicating that the treatment is working.

[0053] After 12 weeks of treatment, the patient's tumor volume has significantly decreased, and the progression of melanoma has been effectively controlled. Gene expression analysis shows that the expression level of TERT has significantly decreased, indicating that the MYC inhibitor effectively inhibits the proliferation and survival of tumor cells. The patient's quality of life has improved significantly, and the side effects are controllable. For example, the patient only experiences mild fatigue and decreased appetite during treatment, and these symptoms gradually subside after stopping medication.

[0054] Through the single-agent treatment strategy targeting MYC, the patient Li's melanoma has been effectively controlled. This case demonstrates the potential of the present application in treating patients with cancer carrying specific genetic combinations, especially those who do not respond well to traditional treatment regimens. Targeting MYC treatment not only significantly inhibits tumor growth but also improves the patient's quality of life, indicating that this method has important value in clinical application.

[0055] In summary, the tumor treatment drug assistance system provided by the present application identifies patients carrying BRAFV600E, TERT promoter mutations, and SNP rs2853669TT through genetic testing and recommends corresponding inhibitors, achieving precise treatment. During treatment, the side effects of medication are controllable, and the patient's quality of life has improved significantly.

[0056] It should be understood that the present application is not limited to the precise construction that has been described above and illustrated in the accompanying drawings, and that various modifications and changes can be made without departing from the scope thereof. The scope of the present application is limited only by the appended claims

[0057] The above description is only the preferred embodiment of the present application, and is not intended to limit the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A tumor treatment medication auxiliary system, characterized in that: Comprising: a marker acquisition module, configured to acquire tumor markers of a patient; a drug recommendation module, configured to give corresponding drug recommendations based on the acquired tumor markers; the drug recommendations include: if the tumor markers contain BRAF V600E mutation, TERT promoter mutation and SNP rs2853669TT, recommending an inhibitor sensitive to tumors carrying the triple gene combination of BRAF V600E mutation, TERT promoter mutation and SNP rs2853669TT; the inhibitor includes: a BRAF inhibitor, a MEK inhibitor, a MYC inhibitor, a RAS inhibitor and a PI3K / AKT inhibitor.

2. The oncology medication assistant system of claim 1, wherein, The drug recommendations also include: if the tumor markers do not contain BRAF V600E mutation, TERT promoter mutation and SNP rs2853669TT, it is not recommended to use the inhibitor.

3. The oncology medication administration assistant system of claim 1, wherein, The BRAF inhibitor includes: GSK2118436A, PLX4032 / RG7204 / RO5185426, CEP-32496 / RXDX-105, RO5126766 / CH5126766 / VS 6766 / CKI-27 / R-7304 / RG-7304, BGB-283, LXH254, HM95573, RAF / KIN_2787, LGX818, PF-07284890, PLX8394 / FORE8394, Everafenib, Uplarafenib, PF-04880594, PF-07799933, PLX7922, PLX-4720, PLX7904, AZ628, AZ304, RAF709, TBAP-001, CCT196969, CCT241161, TAK632, LY3009120, BI-882370, GDC-0879, L-779450, HG6-64-1, Vem-L-Cy5, LUT014, ARQ-736, BGB-3245, SB-590885, SHR902275, GNE-9815, AD57, AD80, NST-628, KG5, ML786dihydrochloride, Takeda-6D and Rafoxanide; The MEK inhibitor includes: AZD6244, HL-085, RDEA119, AS703026, PD0325901, GSK1120212, MEK162, GDC-0973, PD0184264 / ATR-002, WX-554, AZD-8330, GDC-0623, CI-1040, TAK733, SL-327, U0126, PD318088, BIX 02188, BIX 02189, PD98059, PD184161, PD184352, E-6201, SHR 7390, RO4987655, REC-4881, PF-07799544, NFX-179, FCN-150, GW284543, CS3006, IMM-1-104, BI3011441, Myricetin, EKB-569, APS-2-79, BI-847325, RO-5126766, AS-703988, CH5126766; the MYC inhibitor includes: MYC degrader 1, MYC-IN-2, MYC-IN-3, MYC-RIBOTAC, Mycro 1, Mycro 2, Mycro 3, MYCMI-6, MYCi361, MYCi975, c-MYC inhibitor 4, c-MYC inhibitor 5, c-MYC inhibitor 6, c-MYC inhibitor 8, c-MYC inhibitor 9, c-MYC inhibitor 10, c-MYC inhibitor 11, c-MYC inhibitor 12, c-MYC inhibitor 13, c-MYC inhibitor 14, c-MYC inhibitor 15, PROTAC c-Myc degrader-1, NTB2R, MYRA-A, DBPR728, MDEG-541, EN4, MY05, 10058-F4, RA-V, NSC308848, rel-AZ5576, NY2267, JY-3-094, TS-2, sAJM589, VPC-70619, WBC100, 6K465, KSI-3716, IZTZ-1, VPC-70063, KJ Pyr 9, Stauprimide, 10074-A4, EP-12, hnRNPK-IN-1, IRES-C11, IZCZ-3, 10074-G5, ML327, m-Se3, C SI86, Antiproliferative agent-64, Lusianthridin, CT113, Anticancer agent 84, PPA24, THZ1 Hydrochloride, THZ1, BAY1238097, AZD5153, CotyleninA, NSC10010 hydrochloride, SYUIQ5, Ro 31-7837, APTO-253 hydrochloride, APTO-253, Anticancer agent 263, g-Sitosterol, A62176 hydrochloride, and OMO-103; The RAS inhibitors include: Sotorasib, Adagrasib Statins, GDC-6036, JDQ443, TNO155, LY3537982, MRTX1133, ASP3082, BI 1701963, TNO155, RLY-1971, Ulixertinib, Binimetinib, Tipifarnib, KRAS G12C-PROTAC, RMC-6236; The PI3K / AKT inhibitor includes: Buparlisib (BKM120), Pilaralisib, Copanlisib, ZSTK474, Alpelisib, Inavolisib, GSK2636771, Idelalisib, Duvelisib, Eganelisib, Dactolisib, Voxtalisib, Capivasertib, Ipatasertib, Miransertib, Borussertib, Everolimus, Sirolimus, Temsirolimus, Ridaforolimus, Sapanisertib, Vistusertib, AKT-PROTAC, CUDC-907.

4. The oncology medication administration assistant system of claim 1, wherein, The tumor carrying the triple genetic combination of BRAF V600E mutation, TERT promoter mutation and SNP rs2853669TT includes: thyroid cancer, melanoma, lung cancer, breast cancer, gastrointestinal tumor and urinary system tumor.

5. The oncology medication assistant system of claim 4, wherein, The thyroid cancer includes: thyroid papillary carcinoma, thyroid follicular carcinoma, thyroid anaplastic carcinoma.

6. The oncology medication assistant system of claim 4, wherein, The lung cancer includes: non-small cell lung cancer, lung adenocarcinoma, small cell lung cancer.

7. A pharmaceutical composition, characterized by, The pharmaceutical composition includes: the inhibitor according to any one of claims 1-6.

8. Use of the pharmaceutical composition according to claim 7 in the preparation of a medicament for treating a tumor carrying the triple genetic combination of BRAF V600E mutation, TERT promoter mutation and SNP rs2853669TT.

9. Use according to claim 8, characterized in that, The tumor carrying the triple genetic combination of BRAF V600E mutation, TERT promoter mutation and SNP rs2853669TT includes: thyroid cancer, melanoma, lung cancer, breast cancer, gastrointestinal tumor and urinary system tumor.

10. A method of eliminating tumor cells carrying a triple combination of BRAF V600E mutation, TERT promoter mutation and SNP rs2853669TT for non-therapeutic purposes, characterized in that, The pharmaceutical composition according to claim 7 is contacted with tumor cells. The pharmaceutical composition according to claim 7 is contacted with tumor cells.

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