DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for papillary renal cell carcinoma — screening already-approved drugs against its 44-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePapillary renal cell carcinoma maps to a 44-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
No approved-drug candidate for papillary renal cell carcinoma is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
endothelial PAS domain protein 1 (EPAS1) — EPAS1 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet furan-2-ylmethyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3H82 · 1.5 Å · ligand N-(furan-2-ylmethyl)-2-nitro-4-(trifluoromethyl)aniline (020). Experimental structure, not a prediction.
What the evidence adds up to
In a series of 395 surgically treated patients, grade was more strongly associated with death from papillary renal cell carcinoma than tumour type (type 1 or 2). Multivariate analysis showed that symptoms, TNM stage group and grade jointly predicted cancer-specific death. A separate meta-analysis of 35,832 patients (6907 papillary, 28,925 clear cell) found that papillary renal cell carcinoma had a better prognosis overall than clear cell renal cell carcinoma (hazard ratio 0.50, 95% CI 0.45 to 0.56). However, in patients with metastatic disease this advantage disappeared: papillary histology showed a non-significant trend toward higher mortality (HR 1.12, 95% CI 0.71–1.76). Type 2 papillary tumours carried a worse prognosis than clear cell tumours (HR 1.69, 95% CI 0.93–3.08), while type 1 papillary tumours had a better prognosis (HR 0.30, 95% CI 0.12–0.73).
A five-gene mRNA signature (CCNB2, IGF2BP3, KIF18A, PTTG1, BUB1) was derived from The Cancer Genome Atlas RNA-seq data and validated in training and testing sets as a predictor of overall survival in papillary renal cell carcinoma. The study did not report response rates or survival numbers for any treatment. A 2022 review noted that front-line therapy for metastatic renal cell carcinoma now uses combinations of immune checkpoint inhibitors and VEGFR-directed therapies, but did not provide papillary-specific outcome data. A single case report described a seven-year-old boy with stage I papillary renal cell carcinoma treated by nephrectomy alone; he was recurrence-free at six months.
What is missing is prospective trial data that stratifies papillary renal cell carcinoma by type (1 vs 2) and by metastatic status, rather than pooling it with clear cell histology. The five-gene signature has not been tested in a clinical trial or linked to a specific treatment. No drug is mentioned in any of these abstracts as having been tested specifically for papillary renal cell carcinoma.
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 · 2011 · 118 citations
Clinical and Pathological Features Associated With Prognosis in Patients With Papillary Renal Cell Carcinoma
AbstractPURPOSE: We determined the clinical and pathological features associated with death from papillary renal cell carcinoma in 395 surgically treated patients. MATERIALS AND METHODS: Papillary renal cell carcinoma tissue slides from each patient were reviewed for type (1 or 2), grade, TNM stage, coagulative tumor necrosis and sarcomatoid differentiation. Associations of clinical and pathological features with death from renal cell carcinoma were evaluated using Cox proportional hazards regression models and summarized by the HR and 95% CI. Cancer specific survival was estimated using the Kaplan-Meier method. RESULTS: Univariate analysis revealed that symptoms, tumor thrombus, tumor size, perinephric/renal sinus fat invasion, 2010 primary tumor classification, regional lymph node involvement, distant metastasis, 2010 TNM stage group, grade, tumor necrosis, sarcomatoid differentiation and papillary renal cell carcinoma type were associated with death from renal cell carcinoma. Grade was more strongly associated with death from renal cell carcinoma than papillary renal cell carcinoma type. Multivariate analysis indicated that symptoms, 2010 TNM stage group and grade jointly were significantly associated with death from renal cell carcinoma. CONCLUSIONS: This large series of patients with papillary renal cell carcinoma reveals features associated with death from renal cell carcinoma and confirms that grade is more predictive of outcome than papillary renal cell carcinoma type.
A comparison of the prognosis of papillary and clear cell renal cell carcinoma
AbstractOBJECTIVE: To compare the prognosis of papillary and clear cell renal cell carcinoma (RCC) in order to determine the optimal follow-up and therapy for patients with RCC. METHODS: A systematic search of Web of Science, EMBASE, Cochrane Library, and PubMed databases was conducted for articles published through July 30, 2018, reporting on a comparison of the prognosis of papillary RCC and clear cell RCC using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: Of 1896 studies, 11 were considered for the evidence synthesis. A total of 35,832 patients were included. Of these patients, 6907 patients were diagnosed with papillary renal cell carcinoma, and 28,925 patients were diagnosed with clear cell renal cell carcinoma. The prognosis of papillary RCC was better than that of clear cell RCC (hazard ratio (HR) = 0.50; 95% confidence interval (CI) 0.45 to 0.56; P < .001; I = 91.9%). A subgroup analysis indicated that papillary RCC was associated with better outcomes (HR = 0.76, 95% CI 0.50-1.16), and a trend toward a higher risk of mortality was observed in patients with metastatic RCC presenting with papillary histology, but the difference was not statistically significant (HR = 1.12, 95% CI 0.71-1.76, P = .085). Pooled data suggested a lack of a significant difference between papillary RCC (p-RCC) type 1 and clear cell RCC (cc-RCC) (HR = 0.30, 95% CI 0.12-0.73, P = .085). The pooled HR for the prognosis of p-RCC type 2 compared to cc-RCC was 1.69 (95% CI 0.93-3.08; P = .032). CONCLUSION: Papillary RCC is associated with better outcomes than clear cell RCC in patients without metastases, but not in patients with metastases. Optimal follow-up or therapy for patients with RCC should be assigned according to the tumor stage and subtype.
A five-gene signature predicts overall survival of patients with papillary renal cell carcinoma
AbstractBACKGROUND: The present study aims to investigate the gene expression changes in papillary renal cell carcinoma(pRCC) and screen several genes and associated pathways of papillary renal cell carcinoma progression. METHODS: The papillary renal cell carcinoma RNA sequencing (RNA-seq) data set was downloaded from TCGA (The Cancer Genome Atlas). We identified the differentially expressed mRNAs between cancer and normal tissues and performed annotation of differentially expressed mRNAs to figure out the functions and pathways they were enriched in. Then, we constructed a risk score that relied on the 5-mRNA. The optimal value for the patients'classification risk level was identified by ROC analysis. The relationship between mRNA expression and prognosis of papillary renal cell carcinoma was evaluated by univariate Cox regression model. The 5-mRNA based risk score was validated in both complete set and testing set. RESULT: In general, the 5-mRNA (CCNB2, IGF2BP3, KIF18A, PTTG1, and BUB1) were identified and validated, which can predict papillary renal cell carcinoma patient survival. This study revealed the 5-mRNA expression profile and the potential function of a single mRNA as a prognostic target for papillary renal cell carcinoma. CONCLUSION: In addition, these findings may have significant implications for potential treatments options and prognosis for patients with papillary renal cell carcinoma.
Front-Line Therapy for Metastatic Renal Cell Carcinoma: A Perspective on the Current Algorithm and Future Directions
AbstractOver the last decade, the treatment paradigm of metastatic renal cell carcinoma has rapidly evolved, with notable changes in the front-line setting. Combination therapies involving the use of either doublet therapy with immune checkpoint inhibitors or combination VEGFR-directed therapies with immune checkpoint inhibitors have significantly improved clinical outcomes, including prolonged overall survival and durable response to treatment. We aim to highlight the Food and Drug Administration-approved front-line therapy options, the navigation of treatment selection, and the future directions of metastatic renal cell carcinoma therapies.
European Journal of Pediatric Surgery · 2004 · 1 citations
Papillary Renal Cell Carcinoma in a Child
AbstractAIM: To report a case of papillary renal cell carcinoma in a pediatric patient. METHOD: A seven-year-old boy complained of hematuria for one year. CT scan showed a mass in the middle zone of the right kidney. Radical nephrectomy was performed without incident. RESULT: Histology of the specimen showed papillary renal cell carcinoma. As the tumor was stage one, no chemotherapy was offered. At follow-up after 6 months the child was without recurrence or metastases. CONCLUSIONS: Papillary renal cell carcinoma is an uncommon kidney tumor in children and in its early stages it can be cured by nephrectomy alone.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
