DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for bladder clear cell adenocarcinoma — 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 clear cell adenocarcinoma 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 clear cell adenocarcinoma 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
androgen receptor (AR) — AR 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 1r,2rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5CJ6 · 2.07 Å · ligand 2-chloro-4-{[(1R,2R)-2-hydroxy-2-methylcyclopentyl]amino}-3-methylbenzonitrile (51Y). Experimental structure, not a prediction.
What the evidence adds up to
Clear cell adenocarcinoma of the bladder is a rare tumour; a 2005 review of the literature identified only 35 reported cases. Two new cases reported in 2019 had a survival range of 14 weeks to 20 months, consistent with the poor prognosis described in earlier reports. No standard systemic therapy has been established for this subtype.
One 2020 case report describes a 40-year-old woman with metastatic clear cell adenocarcinoma of the urethra who received genetic testing to guide chemotherapy. She was treated with paclitaxel and bevacizumab, a non-platinum regimen. After three cycles she had significant clinical improvement and a definite improvement in size and metabolic activity on PET imaging. She achieved a complete response after six cycles. After 11 cycles, a PET scan confirmed disease progression. She then received two cycles of doxorubicin, which produced a mixed response. This is a single case, not a controlled trial.
A 2021 case report describes a patient with advanced primary clear cell adenocarcinoma of the urethra who had a dramatic and almost complete response to anti-PD-1 immunotherapy in the fourth-line setting. The authors note this is the first such case reported and that there is no high-level evidence to guide treatment for these rare tumours. Localised disease is typically treated with surgery or concurrent chemo-radiotherapy.
For non-muscle-invasive bladder cancer generally, a 2009 review found that a single immediate intravesical chemotherapy instillation after transurethral resection reduces recurrence by 39%, with a number needed to treat of 8.5 to prevent one recurrence. However, this review does not address clear cell adenocarcinoma specifically, and no new instillation agents were added in that period. What remains missing for clear cell adenocarcinoma of the bladder are prospective trials, any randomised data, and a clear molecular stratification that could guide therapy beyond single-case reports.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Scandinavian Journal of Urology and Nephrology · 2005 · 27 citations
Clear cell adenocarcinoma of the urinary bladder
AbstractClear cell adenocarcinoma of the lower urinary tract, and particularly of the bladder, is a rare neoplasm and its histogenesis remains obscure. The authors report the clinical and pathologic findings of a 55-year-old male with clear cell carcinoma of the bladder. The histogenesis of the tumor is discussed, and 35 cases reported in the literature are reviewed.
World Journal of Clinical Oncology · 2020 · 5 citations · open access
Personalized chemotherapy in clear cell adenocarcinoma of the urethra: A case report
AbstractBACKGROUND: Clear cell adenocarcinoma of the urethra is a rare type of aggressive cancer with a poor prognosis. Clear cell carcinoma of the urethra represents less than 0.02% of all malignancies in women. Adenocarcinomas account for 10% of female urethral carcinomas, of which 40% are the clear cell variant. Determining the presence or absence of certain mutations through genetic testing may predict whether a patient with cancer may benefit from a particular chemotherapy regimen. CASE SUMMARY: A 40-year-old woman presented with a 3-year history of slow urinary flow and a 3-mo history of urinary urgency and frequency as well as gross hematuria. An abdominal and pelvic computed tomography scan demonstrated enlarged lymph nodes in the abdomen and pelvis. A biopsy of a left inguinal lymph node microscopically confirmed a metastatic adenocarcinoma of the urethra. Specialized genetic testing determined personalized chemotherapy. She was treated successfully with a non-platinum-based chemotherapy consisting of paclitaxel and bevacizumab. Following 3 cycles of paclitaxel and bevacizumab, she attained significant clinical improvement, and response by FDG-Positron emission tomography (PET) imaging showed a definite improvement in size and metabolic activity. She achieved complete response after 6 cycles of therapy by PET scan. The patient concluded 11 cycles of paclitaxel and bevacizumab, and a subsequent PET scan confirmed progression of metastatic disease. The patient was then treated with two cycles of doxorubicin after which a PET scan revealed a mixed response to the treatment. CONCLUSION: We report the first case of a patient with metastatic clear cell adenocarcinoma of the urethra who underwent personalized chemotherapy after testing for cancer gene alterations. Our unique case represents the safe and effective use of non-platinum-based chemotherapy in clear cell adenocarcinoma of the urethra.
Perioperative instillation therapy in superficial bladder cancer: is it effective regarding outcome and costs?
AbstractPURPOSE OF REVIEW: This article reviews the current knowledge concerning immediate intravesical instillation therapy in nonmuscle-invasive bladder cancer after transurethral resection of the bladder tumour, with emphasis on the literature of the last few years. RECENT FINDINGS: A review was conducted on the recent literature available by PubMed database on the subject of immediate bladder chemotherapy after transurethral resection of the bladder tumour and its recent developments. SUMMARY: A single immediate bladder instillation with chemotherapy will give 39% reduction of recurrence. Numbers needed to treat to prevent one recurrence are estimated at 8.5. In intermediate and high-risk bladder cancer, the immediate postoperative instillation does not give sufficient reduction in recurrence rate to leave out subsequent bladder instillations. The significant reduction of recurrences, the mild side-effects of the treatment and the clear cost-effectiveness make one immediate instillation a valuable addition to transurethral resection of the bladder tumour in the treatment of nonmuscle-invasive bladder cancer. Points of controversy are the true numbers needed to treat to prevent a recurrence and the type of recurrences that will be prevented. No new types of instillation are added recently to the ones available, but promising types are under investigation of which pharmacokinetic studies have shown acceptable rates of side-effects.
Clear cell urethral adenocarcinoma – a case report of an exceptional response to immunotherapy in a metastatic rare tumour
AbstractPrimary clear cell adenocarcinoma of the urethra is extremely rare. Given the rarity of these tumours there is no high-level evidence available to guide treatments. Localized disease is typically treated with primary surgery or concurrent chemo-radiotherapy. In the advanced disease setting treatment options are limited and decisions are based on evidence in disease subtypes where similarities exist. Immuno-oncology and the use of checkpoint inhibitors, particularly for metastatic disease has transformed clinical practice over the past few years and patient outcomes continue to improve as a result of their introduction. Here we report the first case, to our knowledge, of a patient with advanced primary clear cell adenocarcinoma of the urethra who had a dramatic and almost complete response to anti-PD-1 therapy in the fourth line setting. Level of evidence: 4
Clinical Research in Urology · 2019 · 0 citations · open access
Primary Clear Cell Carcinoma of the Bladder: Two New Case Reports and Review of the Literature
AbstractClear cell carcinoma is a very uncommon tumor of the bladder with few cases reported. It may present with hematuria, hydronephrosis, and renal failure. The immunohistochemistry is necessary for the diagnosis. The treatment recommended is radical cystectomy with urinary diversion. The survival range is from 14 weeks to 20 months according to the literature. The objective of this publication is to report two new cases of clear cell carcinoma of the bladder and review the literature.
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.
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