DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for renal carcinoma — screening already-approved drugs against its 42-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleRenal carcinoma maps to a 42-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
approvedAxitinibVascular endothelial growth factor receptor inhibitorapprovedMedroxyprogesterone AcetateApproved drug
Structures already discussed alongside renal carcinoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
CRYSTAL STRUCTURE OF THE VEGFR2 KINASE DOMAIN — Axitinib has a real, experimentally solved structure in complex with this target (PDB 4AG8, 1.95 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet axidrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4AG8 · 1.95 Å · ligand Axitinib (AXI). Experimental structure, not a prediction.
What the evidence adds up to
In a subgroup analysis of Japanese patients from the global AXIS trial, 25 patients received axitinib and 29 received sorafenib after one prior systemic therapy for metastatic renal cell carcinoma. Median progression-free survival was 12.1 months for axitinib versus 4.9 months for sorafenib (hazard ratio 0.390; p = 0.0401). Objective response rate was 52.0% for axitinib and 3.4% for sorafenib (p = 0.0001). Common adverse events with axitinib included dysphonia (68%), hypertension (64%), hand-foot syndrome (64%) and diarrhoea (56%). A separate exploratory subgroup analysis of first-line Asian patients from a phase III trial assigned 48 patients to axitinib and 24 to sorafenib. The hazard ratio for progression-free survival was 0.652 (p = 0.0989), objective response rate was 35.4% versus 16.7% (p = 0.0495), and overall survival hazard ratio was 0.739 (p = 0.1683). Palmar-plantar erythrodysesthesia (57.4%), diarrhoea (55.3%) and hypertension (51.1%) were the most common adverse events with axitinib.
A Japanese subgroup analysis of a randomised phase II study of first-line axitinib with or without dose titration included 44 Japanese and 169 non-Japanese treatment-naïve patients. Objective response rate was 66% (95% CI 50-80%) in Japanese patients versus 44% (95% CI 36-52%) in non-Japanese patients. Median progression-free survival could not be estimated at primary analysis for Japanese patients; an updated analysis gave 27.6 months (95% CI 16.6-33.2). Common adverse events in Japanese patients included hypertension, diarrhoea, hand-foot syndrome, dysphonia, hypothyroidism and proteinuria. Effects of dose titration could not be sufficiently confirmed due to small numbers. Multivariate analysis identified time from diagnosis to treatment and sum of longest diameter of target lesions as independent predictive factors for progression-free survival.
Medroxyprogesterone acetate was given to 23 patients with metastatic renal cell carcinoma in a 1968 study. Among 21 evaluable patients, there was one complete and two partial objective remissions with parenteral preparations; no responses were seen with the oral preparation. Dose to response ranged from 5.2 to 9.0 grams, and response duration from 4 to 30+ months. Eleven patients who progressed on medroxyprogesterone acetate then received testosterone, with one partial response lasting 5 months. A 1983 study measured progesterone receptor in eight renal cell carcinoma samples; receptor was present in all but one. Three receptor-positive patients were treated with medroxyprogesterone acetate, and one had a partial objective response. A 1977 in vitro study using tumour cells from a patient who had responded to medroxyprogesterone acetate found no growth inhibition at therapeutic or pharmacologic levels, suggesting the drug's effect is not due to direct inhibition of renal cell carcinoma growth.
What is still missing is prospective confirmation of predictive biomarkers for axitinib response, particularly in non-Japanese populations, and clarification of whether dose titration provides benefit. For medroxyprogesterone acetate, the mechanism of any occasional response remains unexplained, and no modern trial has tested it against contemporary standards or in a biomarker-selected population. No trial has directly compared axitinib with medroxyprogesterone acetate.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Japanese Journal of Clinical Oncology · 2013 · 71 citations · open access
Efficacy and Safety of Axitinib Versus Sorafenib in Metastatic Renal Cell Carcinoma: Subgroup Analysis of Japanese Patients from the Global Randomized Phase 3 AXIS Trial
AbstractOBJECTIVE: Axitinib is a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2 and 3. The efficacy and safety of axitinib in Japanese patients with metastatic renal cell carcinoma were evaluated. METHODS: A subgroup analysis was conducted in Japanese patients enrolled in the randomized Phase III trial of axitinib versus sorafenib after failure of one prior systemic therapy for metastatic renal cell carcinoma. RESULTS: Twenty-five (of 361) and 29 (of 362) patients randomized to the axitinib and sorafenib arms, respectively, were Japanese and included in this analysis. Median progression-free survival in Japanese patients was 12.1 months (95% confidence interval 8.6 to not estimable) for axitinib and 4.9 months (95% confidence interval 2.8-6.6) for sorafenib (hazard ratio 0.390; 95% confidence interval 0.130-1.173; stratified one-sided P = 0.0401). The objective response rate was 52.0% for axitinib and 3.4% for sorafenib (P = 0.0001). The common all-causality adverse events (all grades) in Japanese patients were dysphonia (68%), hypertension (64%), hand-foot syndrome (64%) and diarrhea (56%) for axitinib, and hand-foot syndrome (86%), hypertension (62%) and diarrhea (52%) for sorafenib. The safety profiles of axitinib and sorafenib in Japanese patients were generally similar to those observed in the overall population, with the exceptions of higher incidences of hypertension, dysphonia, hand-foot syndrome, hypothyroidism and stomatitis. CONCLUSIONS: Axitinib is efficacious and well tolerated in Japanese patients with previously treated metastatic renal cell carcinoma, consistent with the results in the overall population, providing a new targeted therapy for these Japanese patients.
Medroxyprogesterone acetate in the treatment of renal cell carcinoma (hypernephroma)
AbstractMedroxyprogesterone acetate, a potent synthetic progestational steroid, was administered to 23 patients with metastatic renal cell carcinoma. Seven patients received 300 mg/d orally. Six patients received 100 mg/d intramuscularly of the commercial preparation Provera. Ten patients were given 400 mg/w intramuscularly of an investigational preparation. Twenty-one patients completed a minimum treatment period of 6 weeks and were considered evaluable. There were one complete and two partial objective remissions to the parenteral preparations. No responses were observed with the oral preparation. The dose to response varied from 5.2 to 9.0 Gm and the duration of response from 4 to 30+ months. There did not appear to be a correlation of response with age, duration of disease, or histologic grade or cell type. A “symptom status” indicating severe disability from disease did adversely affect response. Minimal side effects were weakness in two patients, loss of libido in one male patient and minimal signs of virilism in one female patient. Eleven patients who showed progressive disease after an adequate trial of medroxyprogesterone acetate received further treatment with testosterone. There was one partial objective response of 5 months' duration. These results are superior to those obtained with chemotherapy.
Axitinib in the Treatment of Metastatic Renal Cell Carcinoma
AbstractAxitinib, an oral small-molecule tyrosine kinase inhibitor targeted to angiogenesis, has demonstrated activity in advanced renal cell carcinoma. Common side effects include hypertension, fatigue and dysphonia. Axitinib is currently awaiting approval as a second-line agent in the treatment of advanced renal cell carcinoma. Trials, which include treatment-naive patients, are ongoing and will study the benefit of axitinib in the first-line setting.
Japanese Journal of Clinical Oncology · 2016 · 23 citations · open access
Key predictive factors for efficacy of axitinib in first-line metastatic renal cell carcinoma: subgroup analysis in Japanese patients from a randomized, double-blind phase II study
AbstractOBJECTIVES: To conduct Japanese subgroup analyses of a randomized, global Phase II study of axitinib with and without dose titration in first-line metastatic renal cell carcinoma and to explore predictive factors for axitinib efficacy in first-line metastatic renal cell carcinoma. METHODS: The data included 44 Japanese and 169 non-Japanese treatment-naïve patients with metastatic renal cell carcinoma. Patients received twice-daily axitinib 5 mg during a 4-week lead-in period. Patients who met the pre-defined randomization criteria were stratified by Eastern Cooperative Oncology Group performance status and randomly assigned (1:1) to axitinib or placebo titration. The primary endpoint was objective response rate; secondary endpoints included progression-free survival and safety. Predictive factors were analyzed using data from all patients. RESULTS: The objective response rate (95% confidence interval) was 66% (50-80%) vs. 44% (36-52%) in Japanese and non-Japanese patients, respectively. At the primary analysis, median progression-free survival could not be estimated for Japanese patients, and was 27.6 months (95% confidence interval: 16.6-33.2) in an updated analysis. Hypertension, diarrhea, hand-foot syndrome, dysphonia, hypothyroidism and proteinuria were common adverse events in Japanese patients. Due to a small number of randomized patients, effects of axitinib dose titration could not sufficiently be confirmed among Japanese patients. The multivariate analysis identified time from histopathological diagnosis to treatment and sum of the longest diameter for target lesion at baseline as independent predictive factors for progression-free survival. CONCLUSIONS: Axitinib is effective and well tolerated as first-line metastatic renal cell carcinoma therapy in Japanese patients. Predictive factors for axitinib efficacy endpoints identified in this setting warrant further investigation.
Journal of Surgical Oncology · 1983 · 18 citations
Measurement of progesterone receptor in human renal cell carcinoma and normal renal tissue
AbstractProgesterone receptor was measured in eight samples of renal cell carcinoma, nine samples of normal renal tissue, and one sample of melanoma tissue. Progesterone receptor was identified in all samples, with the exception of one renal cell carcinoma. Three patients, all with receptor-positive tumors, were treated with medroxyprogesterone acetate for metastatic disease. In one of these patients there was a partial objective response to treatment. Further research regarding progesterone receptor in renal cell carcinoma is indicated.
First-Line Axitinib Versus Sorafenib in Asian Patients with Metastatic Renal Cell Carcinoma: Exploratory Subgroup Analyses of Phase III Data
AbstractAIM: Efficacy/safety of first-line axitinib in Asian patients with metastatic renal cell carcinoma. METHODS: Patients were assigned (2:1) to 5-mg axitinib (n = 48) or 400-mg sorafenib (n = 24) twice daily. Primary end point was progression-free survival. Objective response rate, overall survival and adverse events were also assessed. RESULTS: For axitinib versus sorafenib, hazard ratio for progression-free survival was 0.652 (95% CI: 0.340-1.252; p = 0.0989), objective response rate was higher (35.4 vs 16.7%; p = 0.0495), overall survival longer (hazard ratio: 0.739; 95% CI: 0.397-1.375; p = 0.1683). Palmar-plantar erythrodysesthesia (57.4%), diarrhea (55.3%), hypertension (51.1%) were commonest adverse events with axitinib; palmar-plantar erythrodysesthesia (50.0%) with sorafenib. CONCLUSION: Axitinib improved efficacy in Asian patients with metastatic renal cell carcinoma; adverse events were consistent with previous findings.
Role of Hormones in Growth Kinetics of Renal Cell Carcinoma in Vitro
AbstractMedroxyprogesterone acetate has been used to treat metastatic renal cell carcinoma largely because of its observed inhibitory effects on the growth of estrogen-induced tumors in male Syrian golden hamsters. The absence to date of any successful, established chemotherapeutic regimen in the management of metastatic renal cell carcinoma has led to the continued application of medroxyprogesterone acetate in the majority of patients with this disease because of the occasional regression witnessed (particularly in male patients) and the absence of untoward side effects. To examine the mechanism of action of medroxyprogesterone acetate renal cell carcinoma tumor cells from a patient who had responded to medroxyprogesterone acetate therapy were established in tissue culture. Cells were cultured in control medium, and in the presence of therapeutic and pharmacologic levels of medroxyprogesterone acetate. Tumor cell growth kinetics were determined by the incorporation of 3H thymidine. There was no growth inhibition effected by medroxyprogesterone acetate at therapeutic or pharmacologic levels. Therefore, the proposed salutary effect of medroxyprogesterone acetate in regression of metastatic renal cell carcinoma results from factors other than direct inhibition of renal cell carcinoma growth.
Medroxyprogesterone in Metastatic Renal Cell Carcinoma
AbstractWe have described a patient in whom complete regression of pulmonary metastases from renal cell carcinoma (RCC) followed treatment with medroxy-progesterone acetate (Depo-Provera). Although the reported rate of objective response to progesterone therapy in RCC is only 10% to 15%, the occasionally dramatic results, especially in men, warrant a trial of this agent. Other more toxic agents have consistently failed to provide significant responses.
Disease module: DeepOracle (Open Targets). Approved indication: ChEMBL drug_indication (max_phase=4). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works, resolved on OpenAlex.
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