DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for bladder carcinoma in situ — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBladder carcinoma in situ maps to a 3-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 carcinoma in situ 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
fibroblast growth factor receptor 3 (FGFR3) — FGFR3 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 acpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4K33 · 2.3405 Å · ligand PHOSPHOMETHYLPHOSPHONIC ACID ADENYLATE ESTER (ACP). Experimental structure, not a prediction.
What the evidence adds up to
Intravesical bacillus Calmette-Guerin (BCG) has been the gold standard for carcinoma in situ of the bladder since the late 1970s. Complete and durable response rates have been reported in more than 70% of patients treated with BCG. However, the optimal therapeutic regimen has not been established, and extending treatment beyond the originally described six-week course has not been shown to improve complete response rates while prolonged administration is associated with adverse side effects. For cases refractory or resistant to BCG, treatment options include intravesical chemotherapy, combined immuno-chemotherapy, and radical cystectomy. Intravesical valrubicin and oral bropirimine have been shown to induce a complete response rate of 21% to 50%, though data on long-term follow-up are forthcoming. Radical cystectomy remains effective therapy for aggressive carcinoma in situ.
The current management of carcinoma in situ is ill defined due to the variable natural history and unpredictable response of this disease to therapy. Some tumour characteristics are associated with more aggressive behaviour and may be predictive of treatment outcome, including carcinoma in situ with associated stage T1 bladder lesions, diffuse and multifocal carcinoma in situ, multiple recurrences with intravesical therapy, and extravesical involvement. A 2003 study of 52 primary transitional cell carcinomas found that advancing tumour grade and pathological stage were accompanied by increasing proliferation indices, but decreasing p27(Kip1) and cyclin D1 expression, with no significant change in cyclin E expression. The G1 cyclin index (sum of the level of expression of cyclins D1 and E) correlated positively with proliferation in superficial but not muscle invasive tumours, and this correlation was stronger when the G1 cyclin index was adjusted for p27(Kip1) expression.
A 2004 review concluded that although there is not a single marker able to predict with accuracy the biological potential of bladder cancer, the most promising markers at that point were deletions of chromosome 9 and the tumour suppressor gene p53. Clinical studies were in progress for other biological molecules such as E-cadherin, protein p120, and telomerase. A 2018 review noted that the pathogenesis of bladder cancer is not yet completely clear, and it is difficult to find suitable biomarkers for early detection, evaluation of prognosis, and surveillance of drug responses.
What is still missing is a single molecular marker or panel of markers that can predict with accuracy which carcinomas in situ will respond to BCG or other intravesical therapies, and which will progress. The optimal regimen for BCG itself remains undefined, and the long-term follow-up data for salvage agents such as valrubicin and bropirimine are not yet mature. Prospective trials that stratify patients by molecular markers such as p53 status, cyclin expression, or chromosome 9 deletions are needed, as are studies that distinguish the different biological forms of carcinoma in situ that complicate therapeutic decisions. Funding for such stratified trials and for the validation of candidate biomarkers in large, multi-centre cohorts is lacking.
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 · 2001 · 49 citations
THE LIMITS OF BACILLUS CALMETTE-GUERIN FOR CARCINOMA IN SITU OF THE BLADDER
AbstractPURPOSE: Historically carcinoma in situ of the bladder has been treated with radical cystectomy based on the aggressive and potentially invasive nature of this disease. The introduction in the late 1970s of intravesical bacillus Calmette-Guerin (BCG) has made this therapy the gold standard in the management of carcinoma in situ. Cases that are refractory or resistant to BCG therapy are a management dilemma with various available treatment options. MATERIALS AND METHODS: A comprehensive literature review of the current management of carcinoma in situ of the bladder was performed using MEDLINE, a review of current urology journals and abstracts from recent urology meetings. Data focused on BCG resistant carcinoma in situ of the bladder and current approaches in use for refractory disease. RESULTS: Complete and durable response rates have been reported in more than 70% of patients with carcinoma in situ who are treated with intravesical BCG. To our knowledge the optimal therapeutic regimen has not been established, although extended periods of treatment beyond the originally described 6-week course have not been shown to improve complete response rates. Prolonged administration of BCG is associated with adverse side effects. Various prognostic indicators of recurrence and progression exist that may identify a subset of cases unlikely to respond favorably to a conservative approach, including carcinoma in situ with associated stage T1 bladder lesions, diffuse and multifocal carcinoma in situ, multiple recurrences with intravesical therapy and extravesical involvement. Current molecular markers may also predict the response of carcinoma in situ to therapy. Treatment options available for BCG refractory carcinoma in situ of the bladder include intravesical chemotherapy, combined immuno-chemotherapy and radical cystectomy. Intravesical valrubicin and oral bropirimine have been shown to induce a complete response rate of 21% to 50%, although data on long-term followup are forthcoming. Radical cystectomy remains effective therapy for aggressive carcinoma in situ of the bladder. CONCLUSIONS: The current management of carcinoma in situ of the bladder is ill defined due to the variable natural history and unpredictable response of this disease to therapy. Controversy exists as to the optimal treatment of carcinoma in situ of the bladder since different forms of carcinoma in situ may exist that complicate therapeutic decisions for appropriate therapy. Some tumor characteristics are associated with more aggressive behavior and may be predictive of treatment outcome.
Molecular Pathology · 2003 · 12 citations · open access
Inverse correlation between high level expression of cyclin E and proliferation index in transitional cell carcinoma of the bladder
AbstractBACKGROUND/AIMS: Overexpression of the G1 cyclins, D1 and E, and/or downregulation of p27(Kip1) allow uncontrolled tumour cell proliferation. This study investigated the relation between these three cell cycle proteins and tumour proliferation in bladder cancer. METHOD: Nuclear expression of cyclin D1, cyclin E, and p27(Kip1) was determined immunohistochemically in 52 primary transitional cell carcinomas, and the Ki-67 proliferation marker was also assessed. For each protein, the percentage of positive tumour cell nuclei was determined and analysed as a continuous variable. RESULTS: Advancing tumour grade and pathological stage were accompanied by increasing proliferation indices, but decreasing p27(Kip1) and cyclin D1 expression, with no significant change in cyclin E expression. Overall, cyclin D1 and E expression did not correlate with proliferation. However, in cyclin D1 overexpressing tumours (> or = 5% nuclei positive), the level of cyclin D1 expression positively correlated with proliferation. The correlation between cyclin E expression and proliferation changed from positive to negative with increasing levels of cyclin E expression, accompanied by a coordinate increase in p27(Kip1) expression. Overall, there was an inverse association between p27(Kip1) expression and proliferation. However, a subset of tumours displayed high proliferation indices despite high p27(Kip1) expression. The G1 cyclin index (sum of the level of expression of cyclins D1 and E) correlated positively with proliferation in superficial but not muscle invasive tumours. This correlation was stronger when the G1 cyclin index was adjusted for p27(Kip1) expression. CONCLUSION: These findings support a role for these proteins in the proliferation, differentiation, and progression of bladder transitional cell carcinomas.
International braz j urol · 2015 · 6 citations · open access
Clinical significance of serum and urinary HER2/neu protein levels in primary non-muscle invasive bladder cancer
AbstractOBJECTIVE: We aimed to compare serum and urinary HER2/neu levels between healthy control group and patients with non-muscle invasive bladder cancer. Additionally, we evaluated relationship of HER2/neu levels with tumor stage, grade, recurrence and progression. MATERIALS AND METHODS: Fourty-four patients with primary non-muscle invasive bladder tumors (Group 2) and 40 healthy control group (Group 1) were included the study. Blood and urinary samples were collected from all patients and HER2/neu levels were measured by ELISA method. Blood and urinary HER2/neu levels and additionally, ratio of urinary HER2/neu levels to urinary creatinine levels were recorded. Demographic data and tumor characteristics were recorded. RESULTS: Mean serum HER2/neu levels were similar between two groups and statistically significant difference wasn't observed. Urinary HER2/neu levels were significantly higher in group 2 than group 1. Ratio of urinary HER2/neu to urinary creatinine was significantly higher in group 2 than group 1, (p=0,021). Serum and urinary HER2/ neu levels were not associated with tumor stage, grade, recurrence and progression while ratio of urinary HER2/neu to urinary creatinin levels were significantly higher in high-grade tumors. HER2/neu, the sensitivity of the test was found to be 20.5%, and the specificity was 97.5%, also for the urinary HER2/neu/urinary creatinine ratio, the sensitivity and specificity of the test were found to be 31.8% and 87.5%, respectively. CONCLUSIONS: Urinary HER2/neu and ratio of urinary creatinine urine were significantly higher in patients with bladder cancer compared to healthy subjects. Large series and controlled studies are needed for use as a tumor marker.
The Clinical Significance of Molecular Markers to Bladder Cancer
AbstractStage and grade of transitional cell carcinoma are currently the most useful tools for taking therapeutic decisions and evaluating the prognosis of bladder cancer patients. However, as there are remarkable differences in biological behavior and "biological potential" of tumors classified in the same stage, it is very difficult to predict which superficial tumors will recur and which tumors will give distant metastases. During the last two decades, the better understanding of the molecular mechanisms involved in carcinogenesis and tumor progression has provided a large number of molecular markers of bladder cancer, with a potential diagnostic and prognostic value. This article reviews comprehensively the molecular role and evaluates the clinical significance and the perspectives of these molecular markers. We concluded that, although at the moment there is not a single marker able to predict with accuracy the biological potential of bladder cancer, the most promising markers, at this point, are deletions of chromosome 9, and the tumor suppressor gene p53. Clinical studies are in progress for the assessment of other biological molecules with prognostic potential, such as the E-cadherin, the protein p120, and the telomerase.
Present situation and progress of experimental study on bladder tumors
AbstractBladder cancer (BC) is the most common malignant tumor of the urinary system, which is associated with high recurrence and mortality rate. The pathogenesis of BC is not yet completely clear, and it’s difficult to find suitable biomarkers for early detection, evaluation of prognosis, and surveillance of drug responses. In this article, we will discuss the pathogenesis of bladder cancer, molecular biomarkers and the newest therapy category.
Key words:
Bladder cancer; Pathogenesis; Molecular biomarkers; Immunotherapy; Individualized treatment
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.
