DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Bladder Squamous Cell Carcinoma — screening already-approved drugs against its 14-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBladder Squamous Cell Carcinoma maps to a 14-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 bladder squamous 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
Fifty-one patients with pure squamous cell carcinoma of the bladder treated between 1958 and 1978 had an overall 5-year survival rate of 16%. Ninety-two per cent of cancer deaths were caused by failure to control local disease; treatment by radiotherapy and elective cystectomy resulted in no long-term survivors. A 2023 case report describes one 65-year-old female patient who was free of disease recurrence and metastasis 10 years after partial cystectomy combined with left ureteral reimplantation. Squamous cell carcinoma of the bladder is described as a rare malignancy prone to early invasion and metastasis with a poor prognosis.
In vitro studies on human bladder cancer cell lines, including transitional cell carcinoma lines, show that sunitinib malate exerts a dose- and time-dependent anti-tumour effect. In one study, sunitinib had IC50 values of 1.74 μmol/L, 4.22 μmol/L, and 3.65 μmol/L against the 5637, T24 and BIU87 cell lines respectively. Sunitinib suppressed expression of cyclin B1, p-Akt, and t-Akt while augmenting expression of cyclin D and pro-apoptotic Bax and Bad in HTB5 cells. Analysis of drug combinations revealed that sunitinib acts in synergy with gemcitabine in HTB5 cells. Another study found that sunitinib suppressed the wound healing process in T24 cells in a concentration-dependent manner. These are all in vitro findings; no clinical trial data for sunitinib in bladder squamous cell carcinoma patients are provided in these abstracts.
A 2025 bioinformatic analysis of bladder carcinoma identified key genes including CDKN2A, PTEN, EGFR, PIK3CA, HRAS, FGFR3, and TP53 implicated across multiple pathways, with significant overlap with head and neck squamous cell carcinoma pathways. Drug interaction analysis suggested potential modulatory effects of sertraline, valproic acid, and hydroxyurea on gene expression patterns, but this is computational prediction only. A 2013 review of small cell carcinoma of the urinary bladder notes that no standard treatment has been proposed due to lack of prospective studies, and concludes that multidisciplinary approaches are needed.
What is still missing: prospective clinical trials testing any specific drug in squamous cell carcinoma of the bladder, patient stratification based on the genetic pathways identified, and funding to move from in vitro observations and case reports to adequately powered studies that can assess whether any agent changes the 16% five-year survival rate seen in historical series.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
British Journal of Urology · 1980 · 36 citations
The Management of Squamous Cell Carcinoma of thue Bladder
AbstractFifty-one patients with pure squamous cell carcinoma of the bladder were treated between 1958 and 1978. The overall 5-year survival rate was 16%. Ninety-two per cent of cancer deaths were caused by failure to control local disease; treatment by radiotherapy and elective cystectomy resulted in no long-term survivors. It is concluded that earlier diagnosis would reduce the number of cases presenting with advanced local disease and that future research should be directed towards adjuvant studies with chemotherapeutic agents known to have activity against bladder cancer.
Korean journal of urology · 2011 · 29 citations · open access
Sunitinib Malate Synergistically Potentiates Anti-Tumor Effect of Gemcitabine in Human Bladder Cancer Cells
AbstractPURPOSE: Sunitinib malate (Sutent; Pfizer, New York, NY, USA) is a highly selective multi-targeted agent and has been reported to have potent anti-tumor effects against various tumors, including renal cell carcinoma and gastrointestinal stromal tumors. In this study, we explored in vitro the anti-tumor effect and related molecular mechanisms of sunitinib malate against human bladder cancer cell lines. We also determined the synergistic anti-tumor effect between sunitinib and conventional cytotoxic drugs, cisplatin and gemcitabine, in bladder cancer cells. MATERIALS AND METHODS: Six human cancer cell lines (HTB5, HTB9, T24, UMUC14, SW1710, and J82) were exposed to an escalating dose of sunitinib alone or in combination with cisplatin/gemcitabine, and the cytotoxic effect of the drugs was examined by CCK-8 assay. The synergistic effect between sunitinib and cisplatin/gemcitabine was determined by the combination index (CI) and clonogenic assay. Alterations in cell cycle (cyclin D, B1), survival (p-Akt, t-Akt), and apoptosis (Bax, Bad) regulator expression were analyzed by Western blotting. RESULTS: Like cisplatin and gemcitabine, sunitinib exerted a dose- and time-dependent anti-tumor effect in bladder cancer cells. However, sunitinib exhibited entirely different sensitivity profiles from cisplatin and gemcitabine. Sunitinib suppressed the expression of cyclin B1, p-Akt, and t-Akt while augmenting the expression of cyclin D and pro-apoptotic Bax and Bad in HTB5 cells. Analysis of the drug combination by the isobolic method and clonogenic assay revealed that sunitinib acts in synergy with gemcitabine in HTB5 cells. CONCLUSIONS: These results indicate that sunitinib malate has a potent anti-tumor effect and may synergistically enhance the anti-tumor effect of gemcitabine in human bladder cancer cells.
Expert Review of Anticancer Therapy · 2013 · 7 citations
Small cell carcinoma of the urinary bladder: a contemporary review with a special focus on bladder-sparing treatments
AbstractSmall cell carcinoma of the urinary bladder (SCCUB) is a rare and aggressive disease. To date, no standard treatment has been proposed due to the lack of prospective studies resulting from the rarity of this disease. Recently published studies of relatively large patient cohorts, however, have shed some light on the management of SCCUB patients. In this article, the authors review the epidemiology, pathogenesis, diagnosis and treatment (based on disease stage), and they then discuss the optimal therapeutic strategy for SCCUB patients, particularly for those with limited, locoregional disease. The authors conclude that multidisciplinary approaches are needed for the optimal management of this aggressive disease. The authors also discuss bladder-sparing approaches for SCCUB patients, compared to those for conventional bladder urothelial carcinoma patients.
Frontiers in Oncology · 2023 · 6 citations · open access
Partial cystectomy for bladder squamous cell carcinoma with a 10-year follow-up: a case report
AbstractSquamous cell carcinoma (SCC) of the bladder is a rare malignancy of the urinary system. It is prone to invasion and metastasis in the early stage and has a poor prognosis. This case reports a 65-year-old female patient with SCC of the bladder who was free of disease recurrence and metastasis 10 years after partial cystectomy (PC) combined with left ureteral reimplantation. The treatment plan and admission of this patient were retrospectively analyzed in order to provide some reference significance for the treatment plan for the SCC of the bladder.
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.
Effects of Sunitinib Malate on Growth of Human Bladder Transitional Cell Line T24 In Vitro
AbstractOBJECTIVE: To investigate the growth-inhibitory effect of sunitinib malate on human bladder transitional cell carcinoma (TCC) in vitro. METHODS: Human bladder TCC cell line T24 was cultured and exposed to graded concentrations of sunitinib malate for 72 hours in vitro to determine the sensitivities to drug. Cell viability was measured by MTT assay. Cell apoptotic morphology was observed by fluorescence microscope following DAPI staining. Band expressions of Fas, Fas ligand, poly (ADP-ribose) polymerase (PARP) and β-actin were analyzed by Western blot. Wound healing process of T24 cells exposed to sunitinib malate was assayed. RESULTS: Sunitinib malate exerted a concentration-dependent and time-dependent inhibitory effect on the T24 cell lines. Fluorescence microscopy showed that small vacuoles appeared in the nuclei of T24 cells and the vacuoles were bigger with higher drug concentrations. The expressions of Fas ligand and PARP in T24 cells treated with sunitinib malate exhibited a concentration-dependent increase. Moreover sunitinib malate suppressed the wound healing process in a concentration-dependent manner. CONCLUSION: Sunitinib malate exerted marked inhibitory activity against bladder cancer cell line T24.
Seminars in Surgical Oncology · 1997 · 2 citations
Future therapies for the treatment of bladder neoplasms
AbstractThe last several decades have witnessed an exponential growth in the understanding of the biology of human neoplasms. As a consequence, a number of new strategies for the treatment of urologic cancers are currently under evaluation. We provide an overview of promising new treatment approaches as they apply to the management of transitional cell carcinoma of the urinary bladder.
Turkish Journal of Surgery · 2025 · 0 citations · open access
Genetic profiling and pathway analysis in bladder carcinoma: Implications for therapeutic targeting
AbstractObjective: Bladder carcinoma represents a significant challenge in oncology due to its heterogeneous molecular nature.This study aimed to identify key genetic factors and molecular pathways involved in bladder carcinoma pathogenesis to facilitate the development of targeted therapies. Material and Methods:The top 30 genes associated with bladder carcinoma were retrieved from the disease gene network database.Comprehensive bioinformatic analysis was performed using various enrichment tools, including gene ontology biological process, cellular component, molecular function analyses, and pathway mapping through WikiPathways and metabolite associations through human metabolome database.Drug interactions were evaluated using DrugMatrix data.Results: Gene ontology analysis revealed significant enrichment of cancer-related biological processes, cellular components, and molecular functions.Pathway analysis identified strong associations with head and neck squamous cell carcinoma, cancer pathways, pleural mesothelioma, endometrial cancer, and bladder cancer pathways.Key genes including CDKN2A, PTEN, EGFR, PIK3CA, HRAS, FGFR3, and TP53 were implicated across multiple pathways.Metabolite analysis showed significant associations with phosphatidylinositol derivatives, highlighting the importance of the PI3K pathway.Drug interaction analysis revealed potential modulatory effects of several compounds including sertraline, valproic acid, and hydroxyurea on gene expression patterns in bladder carcinoma. Conclusion:This study provides comprehensive insights into the molecular underpinnings of bladder carcinoma, highlighting interconnected pathways and potential therapeutic targets.The significant overlap with other cancer types suggests common oncogenic mechanisms that could be exploited for therapeutic intervention.Further validation of these findings in clinical samples may facilitate the development of personalized treatment approaches for bladder carcinoma patients.
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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