DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for nonpapillary 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 moduleNonpapillary 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
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ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
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Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Structures already discussed alongside nonpapillary 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 series of 82 patients with small renal masses (≤4 cm) initially managed by active surveillance, median tumour diameter at presentation was 2.0 cm and median delay before intervention was 14 months. Among 87 tumours, 76% eventually received nephron-sparing surgery and 60% were treated minimally invasively. Pathology confirmed renal cell carcinoma in 84% of treated tumours. Of 54 surgically excised tumours, 26% were classified as high-risk and 6% were upstaged on final pathology. The authors concluded that most small sporadic renal tumours grow slowly and that a period of cautious delay does not appear to limit treatment options or increase the risk of progression.
A 2011 study of 395 surgically treated papillary renal cell carcinoma patients found that on multivariate analysis, symptoms at presentation, 2010 TNM stage group, and tumour grade were jointly and significantly associated with death from renal cell carcinoma. Grade was more strongly associated with death than papillary type (type 1 vs type 2). The study confirmed that grade is more predictive of outcome than histological subtype in papillary renal cell carcinoma.
A 2025 retrospective multicentre analysis from Germany included 131 patients with advanced or metastatic papillary renal cell carcinoma. Median age was 63 years, 82% were male, and 70% had ECOG 0–1. First-line therapy was an immune-oncology combination in 52% of patients (IO-IO 18%, TKI-IO 34%) and TKI monotherapy in 40% (mostly sunitinib). Overall response rate for all therapies was 34% (35% for IO-IO, 40% for TKI-IO, 31% for TKI monotherapy). Median progression-free survival was 8.5 months overall (4.9 months for IO-IO, 9.2 months for TKI-IO, 9.0 months for TKI monotherapy). Median overall survival was 32.1 months overall (15.6 months for IO-IO, not reached for TKI-IO, 27.6 months for TKI monotherapy). Adverse events of any grade occurred in 86% of patients on IO-based therapy and 74% on TKI monotherapy; grade ≥3 events occurred in 46% and 22%, respectively. The authors noted major limitations including retrospective data capture and short follow-up (median 19 months), and stated that additional analyses are needed to tailor treatment strategies.
Earlier reviews (2003, 2008) note that renal cell carcinoma is resistant to conventional radiotherapy and chemotherapy, that 5-year survival once metastasised rarely exceeds 20% despite systemic therapy, and that targeted therapies directed against specific biological targets had entered routine use but many questions remained about how best to integrate them. What is still missing are prospective trials with longer follow-up specifically for papillary renal cell carcinoma, reliable biomarkers to stratify patients by likely response, and adequate funding for rare cancer subtypes where commercial incentives are limited.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cancer · 2008 · 120 citations · open access
Delayed intervention of sporadic renal masses undergoing active surveillance
AbstractBACKGROUND: Prompt surgical management remains the standard of care for renal cell carcinoma (RCC). Occasionally, it is necessary to postpone or delay surgical treatment. The authors of this report assessed whether delayed intervention following a period of active surveillance altered minimally invasive or nephron-sparing treatment plans, increased the risk of stage progression, and/or decreased recurrence-free survival rates. METHODS: The authors searched their institutional kidney cancer database to identify small (< or =4 cm in greatest dimension on presentation), enhancing renal masses for which treatment initially was delayed or refused. Clinical, radiographic, and pathologic records were reviewed to determine linear tumor growth kinetics, alterations in treatment plan, stage migration, and cancer-specific outcomes related to delayed intervention. RESULTS: Eighty-seven sporadic, localized, enhancing renal masses were identified in 82 patients who had management postponed for a median of 14 months (mean, 21 months; range, 6-97 months). Median tumor diameter was 2.0 cm on presentation. Treatment in 60 of 87 tumors (69%) was delayed for > or =12 months, and treatment was delayed for > or =24 months in 29 of 87 tumors (33%). Overall, 66 of 87 tumors (76%) underwent nephron-sparing approaches. In addition, 52 of 87 tumors (60%) were treated in a minimally invasive fashion. Pathology confirmed RCC in 73 of 87 treated tumors (84%). Fourteen of 54 tumors (26%) that were treated by surgical extirpation were high-risk tumors, and 3 of 54 tumors (6%) were upstaged on pathologic review. CONCLUSIONS: The majority of small, sporadic, clinically localized renal tumors demonstrated slow interval growth. The management of these lesions may be delayed cautiously without limiting or complicating the available treatment options or incurring a high risk of disease progression.
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.
Expert Review of Molecular Diagnostics · 2008 · 16 citations
Management of metastatic renal cell carcinoma: current trends
AbstractRenal cell carcinoma is one of the common malignancies of the genitourinary tract. In approximately one third of patients, distant metastases are present at the time of initial diagnosis and in another third, the tumor will recur even after nephrectomy with a curative intent. Renal cell carcinoma is resistant to all conventional treatment modalities of cancer, including radiotherapy and chemotherapy. We review the management of patients with metastatic renal cell carcinoma in the era of the new targeted therapeutic agents.
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.
Targeted Therapies in the Treatment of Renal Cell Carcinoma
AbstractThe management of renal cell carcinoma (RCC) has undergone rapid and radical evolution over the last few years. An improved understanding of the underlying biology of RCC has led to the approval of several new therapies directed against specific and relevant biological targets, so-called "targeted therapies." These highly effective treatments are now entering routine use, however many questions still remain as to how best to use these agents and integrate them into the broader therapeutic armamentarium. This review summarizes the major published clinical trials of the new agents, discusses the controversies and research questions that have arisen as a result, and considers some of the issues that remain.
Frontiers in Oncology · 2022 · 5 citations · open access
Renal Abscess Caused by Crizotinib: A Rare Case Report
AbstractCrizotinib is a tyrosine kinase inhibitor that has been found to be effective in the treatment of c-ros oncogene 1-positive non-small cell lung cancer. Although this targeted agent for treating cancer has shown superiority to standard chemotherapy in some ways, this drug has adverse effects, such as the development of renal abscesses. Some associated renal damage may disappear with crizotinib withdrawal. Hence, we present the case of a 58-year-old man with non-small cell lung cancer on crizotinib therapy who developed bilateral renal abnormal space-occupying lesions, successively which were difficult to identify using various imaging methods; even PET-CT highly suspected the right renal masses as malignant. Finally, the right renal lesions were confirmed as renal abscesses by postoperative pathology. The left renal lesion was considered as renal cysts through the lesion disappearing after crizotinib withdrawal. There have been very few reports in this respect, especially proved by various methods and confirmed by postoperative pathology. It is important to recognize this drug-related complication in order to avoid incorrect diagnosis and inadequate therapy. It is necessary to monitor renal changes after taking crizotinib.
Real world evidence from a retrospective multi-center analysis on first-line therapy for metastatic papillary renal cell carcinoma: A GUARDIANS project.
Abstract496 Background: Papillary (pRCC) renal cell carcinoma is a rare cancer. We evaluated real-world treatment outcomes of 1st line treatment in these cohorts in Germany. Methods: Data were collected retrospectively from 13 GU cancer centres in Germany. Patients (pts) with advanced or metastatic pRCC were eligible. Adverse events (AEs) were reported according to CTCAE 5.0. ORR was accessed according to local standard. Progression Free Survival (PFS) were calculated from start of treatment to progression or death. Descriptive statistics and KM-plots were utilized, where appropriate. Results: 131 suitable pts (82% male) with median age of 63 years (range 22-86) were included. ECOG 0-1 was 70%, nephrectomy was performed in 78%. IMDC scores were: 0 in 18%, ≥ 1 in 53%, missing in 29%. The most common sites of metastasis were lymphatic (66%) and pulmonary (41%) metastases. 52% patients received first-line IO-combinations (IO-IO: 18%, TKI-IO: 34%) and 40% patients TKI-monotherapy, predominantly sunitinib. AEs (all grades) with IO‐based or TKI mono therapy, were reported in 86% and 74%, CTCAE grade ≥ 3 in 46% and 22%, dose modifications were required in 35% and 26.0%. ORR and survival outcomes with median follow-up of 19 months (IQR 9-35) are described in the table. Conclusions: TKI-based therapy are frequently applied in pRCC. Our data support the use of IO+ TKI as a first-line standard for patients with pRCC. Major limitations were the retrospective data capture and short follow-up of our study. Additional analyses to tailor treatment strategies in patients with metastatic pRCC is warranted. ORR and survival outcomes of study population. Parameter All therapiesN=131 IO-ION=23 IO-TKIN=45 TKI monoN=51 OtherN=12 ORR (CR+PR) 34% 35 % 40 % 31 % 8% SD 29% 17 % 33 % 29 % 17% PD 23% 35 % 13 % 29 % 17% unknown 14% 13% 13 % 10 % 58 % mOS, months,95%-CI 32 .1 (24.4-39.9) 15.6(7.5-23.7) Not reached 27.6(19.7-35.7) 32.1(21.15-42.7) mPFS, months,95%-CI 8.5(6.5-10.4) 4.9(0.5-9.4) 9.2(3.5-15.0) 9.0(6.9-11.1) 8.5(0.0-22.8)
Are tyrosine kinase inhibitors fit for purpose in the treatment of metastatic papillary renal cell carcinoma?
AbstractRenal cell carcinoma encompasses a range of histological subtypes. The treatment of metastatic disease in this context remains challenging. Papillary renal cell carcinoma is the second most common subtype and forms a significant subsection of non-clear cell renal cell carcinoma. Tyrosine kinase inhibitors form a significant part of the treatment of this largely incurable disease; however, outcomes tend to be poor. The aim of this article is to scrutinise whether these treatments are evidence-based in their use for metastatic papillary renal cell carcinoma and if good outcomes are reported. A literature review was made using PubMed of major prospective and retrospective studies. The European Association of Urology and European Society of Medical Oncology have both published guidance suggesting sunitinib should be offered first line in the treatment of metastatic papillary renal cell carcinoma. This, however, is based upon weak evidence produced by the ASPEN trial, although this did not discriminate between non-clear cell subtypes and results in further studies were modest. The National Institute for Care and Health Excellence has recently published new guidelines for the use of cabozantinib, which has shown evidence of improved progression-free survival and overall response rates compared with sunitinib. Unfortunately, many of the relevant studies did not specifically assess these treatments in patients solely with papillary renal cell carcinoma and had modest overall success. There is weak evidence that tyrosine kinase inhibitors give significant benefit in those patients with metastatic papillary renal cell carcinoma. Level of evidence: 2a
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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