DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for bladder papillary urothelial 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 papillary urothelial 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
No approved-drug candidate for bladder papillary urothelial 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
lysine demethylase 6A (KDM6A) — KDM6A 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 e7zdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6FUL · 1.649 Å · ligand 1-methyl-5-oxidanyl-4-oxidanylidene-pyridine-2-carboxylic acid (E7Z). Experimental structure, not a prediction.
What the evidence adds up to
A 2010 retrospective study of 1,515 patients with primary non-muscle-invasive urothelial tumours (pTa, 1,006 patients; pT1, 509 patients) classified them according to the 2004 WHO/ISUP grading system: 212 cases of papillary urothelial neoplasm of low malignant potential (PUNLMP), 706 low-grade papillary urothelial carcinomas (LPUCs), and 597 high-grade papillary urothelial carcinomas (HPUCs). PUNLMP showed the statistically significantly lowest recurrence cumulative incidence compared with the other tumour types. There were significant differences and trends for higher progression and cancer-specific mortality cumulative incidence in the order: PUNLMP, LPUC, pTa HPUC, and pT1 HPUC. No differences in progression or cancer-specific mortality were found between pTa and pT1 LPUC.
A 2012 review states that for metastatic bladder cancer, median survival is approximately 12–14 months in good prognosis patients, with cure in only a minority. The addition of new drugs to standard cisplatin-based regimens has not improved these figures. Several targeted agents — antiangiogenics, anti-EGFR agents, and immunomodulatory agents — have yet to demonstrate an improvement in overall survival. The review concludes that no major advances have been achieved in recent years and that chemotherapy remains the mainstay of treatment.
A 2009 interim report of 25 patients in a double-blind study comparing lonidamine plus adriamycin to adriamycin alone in the adjuvant treatment of recurrent papillary carcinomas states that it is impossible to draw any conclusion on therapeutic activity, though tolerance was judged satisfactory. A 2016 paper notes that bladder micropapillary carcinoma, restricted to less than 10% of urothelial cell carcinoma, is associated with shorter survival due to early and wide metastatic chemoresistant spread. A 2020 case series reports that in high-grade tumours involving the urinary tract, the presence of papillary or pseudopapillary morphology is not sufficient to render a diagnosis of papillary urothelial carcinoma; prostate adenocarcinoma, primary bladder adenocarcinoma, or metastasis must be excluded (3% of cases in a 42-month period).
What is still missing are large, randomised trials that demonstrate a survival benefit for any targeted or combination therapy over standard chemotherapy in the metastatic setting. The molecular pathology and biomarker literature (2011) remains largely descriptive, without validated predictive biomarkers that can stratify patients for treatment. The 2009 lonidamine trial is too small to draw conclusions, and no subsequent large-scale data for that combination have been reported. Patient stratification by the 2004 WHO/ISUP system is validated for non-muscle-invasive disease, but its utility for guiding therapy in advanced or recurrent disease has not been established in prospective 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.
American Journal of Clinical Pathology · 2010 · 148 citations · open access
Prognostic Significance of the 2004 WHO/ISUP Classification for Prediction of Recurrence, Progression, and Cancer-Specific Mortality of Non–Muscle-Invasive Urothelial Tumors of the Urinary Bladder
AbstractTo verify prognostic significance of the 2004 World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading systems, we retrospectively studied the tumors of 1,515 patients who underwent transurethral resection of primary non-muscle-invasive urothelial tumors (pTa, 1,006 patients; pT1, 509 patients) confined to the bladder. Cases were classified according to the 2004 WHO/ISUP systems as 212 cases of papillary urothelial neoplasm of low malignant potential (PUNLMP), 706 low-grade papillary urothelial carcinomas (LPUCs), and 597 high-grade papillary urothelial carcinomas (HPUCs). PUNLMP showed the statistically significantly lowest recurrence cumulative incidence compared with the other tumor types. There were significant differences and trends for higher progression and cancer-specific mortality cumulative incidence in the following order: PUNLMP, LPUC, pTa HPUC, and pT1 HPUC. No differences of progression and cancer-specific mortality cumulative incidence were found between pTa and pT1 LPUC. Our study validates the usefulness of the 2004 WHO/ISUP system to classify urothelial tumors into prognostically distinct categories that would contribute to the design of therapeutic and monitoring strategies for patients with non-muscle-invasive bladder urothelial tumors.
Current Opinion in Supportive and Palliative Care · 2012 · 15 citations
Metastatic bladder cancer
AbstractPURPOSE OF REVIEW: Although bladder cancer is considered a chemosensitive disease, the prognosis of patients with metastatic disease is still poor with median survival being approximately 12-14 months in good prognosis patients and with cure in only a minority of patients. The addition of new drugs to the standard cisplatin-based regimens has not improved these figures. The purpose of this review is to highlight the role of chemotherapy and the impact of the new targeted agents in the treatment of metastatic bladder carcinoma. RECENT FINDINGS: A better understanding of the biology of the molecular patterns of urothelial bladder cancer has led to the clinical investigation of several therapeutic targets such as antiangiogenics, anti-EGFR agents, and immunomodulatory agents. To date, these agents have yet to demonstrate an improvement in overall survival. The molecular alterations that drive platinum resistance and the study of the genetic profiles will help to identify the prognostic and predictive biomarkers. SUMMARY: No major advances have been achieved in the recent years in the treatment of urothelial carcinoma of the bladder. Chemotherapy remains the mainstay of treatment of metastatic disease. Several targeted agents are currently under investigation, but no major breakthroughs have been achieved with these drugs. Development of less toxic, more effective agents is crucial and clinical trial participation needs to be emphasized.
Cancer Biomarkers · 2011 · 15 citations · open access
Molecular pathology and biomarkers of bladder cancer
AbstractBladder cancer originates in the epithelial lining of the bladder's mucosa and develops in association with several habitual, industrial, and environmental risk factors via papillary and non-papillary pathways. In this chapter we review novel concepts concerning the molecular mechanisms of early field change in bladder neoplasia stemming from whole-organ genomic mapping studies. These mechanisms are discussed in the context of molecular pathogenesis of bladder cancer and in relation to treatment and biomarker-based detection strategies.
Lonidamine plus Adriamycin versus Adriamycin Alone in the Adjuvant Treatment of Recurrent Papillary Carcinomas of the Urinary Bladder
AbstractThis paper reports the interim results of 25 patients included in a double-blind study in which the combination of Lonidamine plus adriamycin is compared to adriamycin alone in the adjuvant treatment of papillary carcinomas of the urinary bladder. Although it is impossible to draw any conclusion at this time on the therapeutic activity of this combination, tolerance was judged satisfactory.
Translational Andrology and Urology · 2016 · 3 citations · open access
The luminal-basal paradigm in the urothelial cancer: hope for individualized approach
AbstractWhile restricted to less than 10% of the urothelial cell carcinoma spectrum, bladder micropapillary carcinoma (MPUC) is associated with shorter survival due to early and wide metastatic chemo resistant spread. Such ominous behavior makes it an interesting model to identify new diagnostic, prognostic, and therapeutic targets based on unique gene expressions and molecular features associated with the aggressive nature of the disease (1).
Surgical and Experimental Pathology · 2020 · 0 citations · open access
Carcinomas in the bladder with papillary and pseudopapillary morphology - not always urothelial
AbstractAbstract Background Urothelial carcinoma shows wide plasticity and broad morphologic spectrum. In many instances, the presence of papillary morphology is reassuring of the urothelial histogenesis of a high-grade invasive lesion but is not pathognomonic. Case presentation We reported herein four cases of carcinomas in the bladder with papillary morphology that had a final diagnosis different from urothelial carcinoma (3% of cases in a 42-month period). In high-grade tumors involving the urinary tract, the presence of papillary/pseudopapillary morphology is not sufficient to render a diagnosis of papillary urothelial carcinoma. Prostate adenocarcinoma, primary bladder adenocarcinoma or metastasis must be excluded in selected case scenarios.
International Journal of Surgery and Medicine · 2019 · 0 citations
Synchronous invasive urothelial cell carcinoma of the bladder with chronic myeloid leukemia
AbstractIncident of bladder carcinoma synchronous with CML was about 0.45% and its treatment became a challenge. We reported a case of invasive urothelial cell carcinoma with chronic myeloid leukemia (CML) in a 55-years-old man. The patient suffered painless gross hematuria from the first time. Patient complained of weight drop drastically and often accompanied by intermittent fever. The result of bone marrow biopsy was chronic phase CML, while the results of abdominal ultrasound and abdominal Multislice Computerized Tomography without contrast were a bladder mass. The patient underwent TUR-BT and therapy with imatinib. The pathology result showed that an Invasive Urothelial Cell Carcinoma of bladder. Our report concluded an uncommon case of Invasive Urothelial Cell Carcinoma of bladder and CML.
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.
