DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for ureter urothelial carcinoma — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleUreter urothelial carcinoma maps to a 4-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
approvedSunitinibApproved drug
Structures already discussed alongside ureter urothelial 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 multi-institutional study of 304 patients with clinically organ-confined distal ureter urothelial carcinoma and bilateral functional kidneys, 128 received radical nephroureterectomy, 134 distal ureterectomy, and 42 endoscopic surgery. Five-year local recurrence-free survival was 95.0% for nephroureterectomy, 85.5% for distal ureterectomy, and 35.7% for endoscopic surgery. Endoscopic surgery was an independent predictor of worse local recurrence-free survival compared to nephroureterectomy (HR 1.27, p=0.001) or distal ureterectomy (HR 1.14, p=0.01). Overall, cancer-specific, and intravesical recurrence-free survival rates were equivalent across the three procedures. After adjustment for ASA score, distal ureterectomy (HR 0.80, p=0.01) and endoscopic surgery (HR 0.84, p=0.02) were independent predictors of increased overall survival, though no significant difference was found between them. The authors concluded that distal ureterectomy could be considered elective first-line treatment for this patient group.
In laboratory work, sunitinib malate was tested against three human bladder transitional cell carcinoma cell lines (5637, T24, BIU87). The drug showed concentration-dependent inhibition with IC50 values of 1.74 μmol/L, 4.22 μmol/L, and 3.65 μmol/L respectively. Cisplatin also showed antitumour activity. Sorafenib suppressed proliferation only at concentrations of 10 μmol/L or higher, with practically no response at lower concentrations. Sunitinib malate treatment led to accumulation of cells in sub-G1 phase and induced apoptosis, particularly in T24 and BIU87 cells. The authors suggested that clinical application of sunitinib-based therapy for advanced bladder cancer is possible, but this remains an in vitro finding only.
A 2019 review described two distinct molecular pathways for non-invasive and invasive urinary tract urothelial carcinoma, and discussed stem marker immunohistochemistry and mechanisms of multifocal and recurrent tumour carcinogenesis. No specific drug or treatment data were presented in that article.
What is still missing: prospective randomised trials comparing distal ureterectomy to nephroureterectomy for distal ureter tumours, with longer follow-up and standardised definitions of local recurrence. For sunitinib, no clinical trial data in ureter urothelial carcinoma patients exist; the in vitro work has not been translated into human studies. The molecular review offers no actionable targets or validated biomarkers for patient stratification. Funding for definitive surgical trials and for any clinical testing of sunitinib in upper tract disease is absent.
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 · 2015 · 46 citations
Oncologic Outcomes of Kidney Sparing Surgery versus Radical Nephroureterectomy for the Elective Treatment of Clinically Organ Confined Upper Tract Urothelial Carcinoma of the Distal Ureter
AbstractPURPOSE: We compared the oncologic outcomes of radical nephroureterectomy, distal ureterectomy and endoscopic surgery for elective treatment of clinically organ confined upper tract urothelial carcinoma of the distal ureter. MATERIALS AND METHODS: From a multi-institutional collaborative database we identified 304 patients with unifocal, clinically organ confined urothelial carcinoma of the distal ureter and bilateral functional kidneys. Rates of overall, cancer specific, local recurrence-free and intravesical recurrence-free survival according to surgery type were compared using Kaplan-Meier statistics. Univariable and multivariable Cox regression analyses were performed to assess the adjusted outcomes of radical nephroureterectomy, distal ureterectomy and endoscopic surgery. RESULTS: Overall 128 (42.1%), 134 (44.1%) and 42 patients (13.8%) were treated with radical nephroureterectomy, distal ureterectomy and endoscopic surgery, respectively. Although rates of overall, cancer specific and intravesical recurrence-free survival were equivalent among the 3 surgical procedures, 5-year local recurrence-free survival was lower for endoscopic surgery (35.7%) than for nephroureterectomy (95.0%, p <0.001) or ureterectomy (85.5%, p = 0.01) with no significant difference between nephroureterectomy and distal ureterectomy. On multivariable analyses only endoscopic surgery was an independent predictor of decreased local recurrence-free survival compared to nephroureterectomy (HR 1.27, p = 0.001) or distal ureterectomy (HR 1.14, p = 0.01). Distal ureterectomy and endoscopic surgery did not significantly correlate to cancer specific or intravesical recurrence-free survival. However, when adjustment was made for ASA(®) (American Society of Anesthesiologists(®)) score, distal ureterectomy (HR 0.80, p = 0.01) and endoscopic surgery (HR 0.84, p = 0.02) were independent predictors of increased overall survival, although no significant difference was found between them. CONCLUSIONS: Because of better oncologic outcomes, distal ureterectomy could be considered the elective first line treatment of clinically organ confined urothelial carcinoma of the distal ureter.
Cancer Cell International · 2015 · 6 citations · open access
Human urothelial carcinoma cell response to Sunitinib malate therapy in vitro
AbstractOBJECTIVES: Bladder transitional cell carcinoma (TCC) is one of the most common solid malignancies in China. This study examined the antitumor effect and underlying mechanism of action of sunitinib malate in human bladder TCC in vitro. METHODS: Bladder TCC cell lines 5637 and BIU87 were maintained in 1640 medium and T24 cell lines in DMEM/F12 medium. All 3 cell lines were then exposed to graded concentrations (0.625-20 μmol/L) of sunitinib malate, sorafenib and cisplatin for 24-96 hours to determine the sensitivities to each drug. Cell viability was measured by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium] assay, and apoptosis was analyzed by flow cytometry. Cell apoptotic morphology was observed by a fluorescence microscope after DAPI (4',6-diamidino-2-phenylindole) staining. Protein concentrations were measured by western blot. RESULTS: Sunitinib malate showed a concentration-dependent inhibitory effect on the 5637, T24 and BIU87 cell lines with IC50's of 1.74 μmol/L, 4.22 μmol/L, and 3.65 μmol/L, respectively. Cisplatin also exhibited good antitumor activity, but whereas sorafenib suppressed proliferation of the cells at concentrations of 10 μmol/L or higher, there was practically no response at lower concentrations. Sunitinib malate treatment resulted in an accumulation of cells in the sub-G1 phase, especially with the T24 and BIU87 cell lines, which induced apoptosis of the cells. CONCLUSIONS: Sunitinib malate exerted marked inhibitory activity against bladder cancer cells. The cell growth inhibitory effect of the drug was related to induction of apoptosis. These results suggest that clinical application of sunitinib-based therapy for advanced bladder cancer is possible.
Molecular basis of intratumoral heterogeneity of urinary tract urothelial carcinoma
AbstractIn the article the main mechanisms of molecular pathogenesis of urinary tract urothelial carcinoma are presented. Two different molecular pathways that determine the development of non-invasive and invasive urothelial carcinoma, the immunohistochemical spectrum of stem markers and aspects of the carcinogenesis of multifocal and recurrent tumors are considered.
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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