DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for renal cell carcinoma — screening already-approved drugs against its 49-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleRenal cell carcinoma maps to a 49-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
Structures already discussed alongside renal cell carcinoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
KIT kinase domain — Sunitinib has a real, experimentally solved structure in complex with this target (PDB 3G0E, 1.6 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 b49drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3G0E · 1.6 Å · ligand Sunitinib (B49). Experimental structure, not a prediction.
What the evidence adds up to
In a 2008 study of 19 patients with advanced renal cell carcinoma whose primary tumour was considered unsuitable for initial nephrectomy, neoadjuvant sunitinib (50 mg daily, 4 weeks on, 2 weeks off) produced no complete responses. Partial responses of the primary tumour occurred in 3 patients (16%), stable disease in 7 (37%), and disease progression in the primary tumour in 9 (47%). Overall, 2 patients (11%) had a partial response, 7 (37%) stable disease, and 10 (53%) disease progression. At a median follow-up of 6 months, 4 patients (21%) had undergone nephrectomy; viable tumour was present in all four specimens. Five patients died of disease progression. Grade 3–4 toxicity occurred in 7 patients (37%), and treatment was discontinued in one due to toxicity.
A 2012 preclinical study tested the CRM1 inhibitors KPT-185 and KPT-251 in renal cell carcinoma cell lines and a xenograft model. KPT-185 increased cytotoxicity in vitro, with evidence of apoptosis and cell cycle arrest, and caused p53 and p21 to remain primarily in the nucleus. In a high-grade xenograft model, oral KPT-251 significantly inhibited tumour growth with no obvious toxicity. The same year, a review of sorafenib stated it was likely to remain a mainstay of renal cell carcinoma treatment, but provided no new numerical data. A 2004 review noted that high-dose interleukin-2 remained the mainstay for metastatic disease but that few patients derived long-term benefit, and cytokine therapy in the adjuvant setting had been disappointing. Bevacizumab and small-molecule inhibitors of angiogenesis were described as emerging.
A 2022 review of tivozanib, approved by the US FDA in March 2021 for relapsed or refractory renal cell carcinoma, described it as an oral, selective VEGFR-1, -2, and -3 tyrosine kinase inhibitor with a long half-life and dose-related controllable hypertension as its most common side effect. The review claimed synergistic antitumour efficacy when blocking VEGF and mTOR pathways simultaneously, but provided no new clinical trial data. A 2015 case report described pazopanib as first-line therapy in a single patient with inoperable kidney cancer, reporting disease stabilisation. A 2003 review discussed early diagnostic approaches (circulating tumour cells, MN/CAIX gene detection, von Hippel-Lindau mutations in urine) and noted that heterozygosity or homozygosity for class II haplotypes DQA1 and DQB1 predicted response and survival after cytokine therapy. A 2014 case report described the development and spontaneous regression of crizotinib-associated complex renal cysts in a single lung cancer patient on continuous crizotinib, but this was not a renal cell carcinoma study.
What is still missing: large-scale, randomised trials directly comparing these agents in defined patient subgroups; prospective validation of molecular markers (CRM1, p53 localisation, HLA haplotypes) to stratify patients; and data on whether neoadjuvant sunitinib or other TKIs improve overall survival rather than just conversion to resectability. The disappointing response rates and toxicity in the sunitinib neoadjuvant study, and the lack of controlled data for tivozanib and pazopanib in the abstracts provided, underscore the need for adequately funded, biomarker-driven trials.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Urology · 2008 · 193 citations
Response of the Primary Tumor to Neoadjuvant Sunitinib in Patients With Advanced Renal Cell Carcinoma
AbstractPURPOSE: We assessed the activity of neoadjuvant sunitinib on primary renal tumors in patients with advanced renal cell carcinoma as well as the feasibility and safety of subsequent surgical resection. METHODS: A total of 19 patients with advanced renal cell carcinoma deemed unsuitable for initial nephrectomy due to locally advanced disease or extensive metastatic burden were treated with 50 mg sunitinib daily for 4 weeks on followed by 2 weeks off. Tumor response was assessed by Response Evaluation Criteria in Solid Tumors every 2 cycles and the rate of conversion to resectable status was estimated. RESULTS: Median patient age was 64 years and initial median radiographic renal tumor size was 10.5 cm. Clinical stage was N+ (10) and M+ (15). No patients experienced a complete response. Partial responses of the primary tumor were noted in 3 patients (16%), 7 (37%) had stable disease and 9 (47%) had disease progression in the primary tumor. Overall tumor response included 2 patients (11%) with partial response, 7 (37%) with stable disease and 10 (53%) with disease progression. At a median followup of 6 months (range 1 to 15) 4 patients (21%) had undergone nephrectomy and 5 died of disease progression. No unexpected surgical morbidity was encountered. Viable tumor was present in all 4 specimens. Sunitinib was associated with grade 3-4 toxicity in 7 patients (37%) and treatment was discontinued in 1 due to toxicity. CONCLUSIONS: Administration of sunitinib in patients with advanced renal cell carcinoma with the primary tumor in place is feasible and can lead to a reduction in tumor burden that can facilitate subsequent surgical resection.
CRM1 Blockade by Selective Inhibitors of Nuclear Export Attenuates Kidney Cancer Growth
AbstractPURPOSE: Renal cell carcinoma often presents asymptomatically and patients are commonly diagnosed at the metastatic stage, when treatment options are limited and survival is poor. Since progression-free survival using current therapy for metastatic renal cell carcinoma is only 1 to 2 years and existing drugs are associated with a high resistance rate, new pharmacological targets are needed. We identified and evaluated the nuclear exporter protein CRM1 as a novel potential therapy for renal cell carcinoma. MATERIALS AND METHODS: We tested the efficacy of the CRM1 inhibitors KPT-185 and 251 in several renal cell carcinoma cell lines and in a renal cell carcinoma xenograft model. Apoptosis and cell cycle arrest were quantified and localization of p53 family proteins was assessed using standard techniques. RESULTS: KPT-185 attenuated CRM1 and showed increased cytotoxicity in renal cell carcinoma cells in vitro with evidence of increased apoptosis as well as cell cycle arrest. KPT-185 caused p53 and p21 to remain primarily in the nucleus in all renal cell carcinoma cell lines, suggesting that the mechanism of action of these compounds depends on tumor suppressor protein localization. Furthermore, when administered orally in a high grade renal cell carcinoma xenograft model, the bioavailable CRM1 inhibitor KPT-251 significantly inhibited tumor growth in vivo with the expected on target effects and no obvious toxicity. CONCLUSIONS: The CRM1 inhibitor protein family is a novel therapeutic target for renal cell carcinoma that deserves further intensive investigation for this and other urological malignancies.
The Oncologist · 2014 · 35 citations · open access
Spontaneous Regression of Crizotinib-Associated Complex Renal Cysts During Continuous Crizotinib Treatment
AbstractThis study describes the development and regression of crizotinib-associated complex renal cysts (CACRCs) in a female patient with ALK-positive advanced non-small cell lung cancer with an ongoing complete response while on continuous crizotinib treatment. The clinical context of crizotinib use requires frequent imaging studies; therefore observation is probably the best approach to CACRC management in asymptomatic patients. The natural history of CACRCs remains unknown, and large-scale longitudinal follow-up studies of these cysts are eagerly awaited.
AbstractPURPOSE OF REVIEW: Renal cell carcinoma continues to be a devastating cancer, which currently has few effective treatment options. Recent developments in our understanding of the molecular biology of renal cell carcinoma, particularly clear cell renal cell carcinoma, have led to the development of new agents targeting portions of the hypoxic response pathway. RECENT FINDINGS: Although high-dose bolus interleukin-2 remains the mainstay of treatment for metastatic disease, the number of patients deriving long-term benefit from this treatment are few, and the use of cytokine therapy in the adjuvant setting has been disappointing. However, the expanding use of minimally invasive surgical techniques has continued to improve patient care. Systemic advances include antibody therapeutics such as bevacizumab, which targets vascular endothelial growth factor signaling, as well as emerging small molecule inhibitors of angiogenesis-related signaling events. SUMMARY: In addition to progress in surgical techniques and supportive care of patients with renal cell carcinoma, a host of promising targeted therapies for renal cell carcinoma are on the horizon.
Anti-Cancer Agents in Medicinal Chemistry · 2022 · 8 citations
Tivozanib: A New Hope for Treating Renal Cell Carcinoma
AbstractBACKGROUND: Renal cell carcinoma (RCC) is a diverse collection of malignancies with varying histological characteristics, molecular changes, prognosis, and therapeutic response. Tivozanib was first approved in March 2021 by USFDA with the brand name Fotivda. Tivozanib hydrochloride monohydrate is an oral medication that is used to treat relapsed or refractory renal cell carcinoma. OBJECTIVE: In this review, we explain renal cell carcinoma and its different types of treatment by the anti-renal carcinoma drugs. METHODS: A comprehensive literature search was conducted in the relevant databases, like ScienceDirect, PubMed, ResearchGate, and Google Scholar, to identify the studies. CONCLUSION: Tivozanib is an oral VEGFR-1, VEGFR-2, and VEGFR-3 tyrosine kinase inhibitor that is extremely selective and powerful. It has much less affinity for other receptor tyrosine kinases than multi-targeted TKIs now in clinical use. Because of its long half-life in circulation, it may be able to block VEGFRs more consistently. Doserelated controllable hypertension is its most commonly seen drug-related side event. Fatigue, hoarseness, and diarrhea, which are all common side effects, are not dose-related. Because of its target specificity, tivozanib can work well with other medications that have low side effects. Blocking both the VEGF and mTOR signaling pathways at the same time provides the benefit of synergistic antitumor efficacy while also preventing treatment resistance. Thus, overall we can say that the drug tivozanib is suitable for treatment in patients with renal cell carcinoma and can be investigated in multi-center clinical trials.
Basic science and research in renal cell carcinoma: from workbench to bedside
AbstractPURPOSE OF REVIEW: Renal cell carcinoma represents the third most common cancer in men. Radical surgery remains the only curative approach, and the 5-year survival rate once the cancer has metastasized rarely exceeds 20% despite systemic therapy. It becomes evident that an improvement in outcome might only be achieved if (1) there is early diagnosis, (2) there is accurate prediction of progression and response, and (3) new treatment options reflecting the molecular pathogenesis and progression are developed. RECENT FINDINGS: The detection of circulating cancer cells by reverse transcriptase/polymerase chain reaction techniques for the MN/CAIX gene, the identification of specific genetic alterations in circulating tumor DNA, as well as the demonstration of somatic von Hippel-Lindau mutations and extracellular matrix proteins in urine of high-risk patients might be clinically useful in improving early diagnosis and treatment. The signal transducer and activator of transcription has been shown to significantly correlate with relapse patterns following radical surgery. Heterozygosity or homozygosity for class II haplotypes DQA1 and DQB1 accurately predicts response and survival following cytokine-based therapy and may be helpful in patient selection. In terms of treatment, the use of monoclonal antibody derivates against the epidermal growth factor receptor and the vascular endothelial growth factor receptor has shown promising clinical results. Antisense oligodeoxynucleotide therapy has shown significant therapeutic effects in in-vitro and in-vivo studies. Recent developments in the clinical application of proteasome inhibitors have opened the door to exciting, highly specific and effective molecular treatment options for metastatic renal cell carcinoma. SUMMARY: Recent developments in research on renal cell carcinoma have identified various clinically useful diagnostic and therapeutic options reflecting the molecular basis of the pathogenesis and progression of the disease.
Cancer Growth and Metastasis · 2012 · 4 citations · open access
Safety and Efficacy of Sorafenib in Renal Cell Carcinoma
AbstractThis article reviews data on sorafenib use in renal cell carcinoma. Mechanisms of actions and pharmacokinetics are briefly described. Major clinical trials are presented, summarizing efficacy and safety of sorafenib. Its place in current treatment of renal cell carcinoma is discussed. Sorafenib is likely to remain one of the mainstays of RCC treatment in coming years.
Malignant tumours · 2015 · 0 citations · open access
Tyrosine kinase inhibitors as a targeted therapy for clear cell renal carcinoma: case report of the intrahepatic bile ducts
AbstractThis article is a result of their own long-term observation of the patient treatment of inoperable cancer of the kidney. As first-line therapy pazopanib is used in standard dosage. The drug belongs to the new generation of drugs that block angiogenesis and having cytoreductive effect. During treatment, the stabilization of the disease. The results of treatment can be recommended for use pazopanib treatment of kidney cancer.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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