DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for bile duct adenocarcinoma — screening already-approved drugs against its 47-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBile duct adenocarcinoma maps to a 47-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 bile duct 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
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
In a retrospective series of 129 patients with bile duct adenocarcinoma treated between 1977 and 1987, median survival was 6.5 months with surgery alone, 11 months with surgery plus conventional adjuvant x-ray radiotherapy, and 14 months with surgery plus charged-particle radiotherapy. Among patients treated with curative intent, median survival was 16 months for surgery alone and for surgery plus conventional radiotherapy, and 23 months for surgery plus charged particles. Patients with microscopic residual disease had longer median survival when given adjuvant irradiation, most markedly with charged particles (p = 0.0005) but also with conventional x-rays (p = 0.0109). For gross residual disease the survival advantage was less marked but still statistically significant. The authors concluded that maximal surgical resection was the mainstay and that postoperative radiotherapy gave a survival advantage to patients with positive microscopic margins.
A separate retrospective review of 23 patients who received salvage radiotherapy for isolated locoregional recurrence after radical surgery reported a median overall survival of 18.4 months and median progression-free survival of 15.5 months. The median disease-free interval before recurrence was 11.8 months. Concomitant chemotherapy was associated with improved progression-free survival on multivariate analysis (p = 0.027), but a disease-free interval of one year or longer was associated with significantly worse overall survival (p = 0.047). No grade 3 or higher toxicities occurred. The authors described the outcomes as promising but noted that the ideal management of locoregional relapse remains undefined.
Molecular studies have shown that distal common bile duct carcinomas lose DPC4 expression in 55% of cases and abnormally express p53 in 51%, rates similar to pancreatic ductal adenocarcinoma. Proximal bile duct carcinomas show loss of DPC4 in only 15% and abnormal p53 in 26%, indicating different molecular mechanisms between proximal and distal tumours. In the distal common bile duct carcinomas, only poorly differentiated histology correlated with decreased survival on multivariate analysis; p53 or Dpc4 labelling, margin status, lymph node status, and tumour dimension did not correlate significantly with survival. A 2009 review noted that despite combined therapeutic strategies the prognosis of cholangiocarcinoma remains poor, that surgery is the only curative modality, and that prospective studies including molecular and genetic markers are needed to improve patient selection and outcomes. The 5-year survival for cholangiocarcinoma depending on location ranges from 27% to 60%, according to a 2017 review of emerging therapies.
What is still missing are prospective trials that stratify patients by tumour location and molecular markers, and that test whether the survival advantages seen in retrospective radiotherapy series hold in controlled settings. The molecular heterogeneity between proximal and distal tumours has not been translated into stratified treatment protocols. Funding for such trials, and for the development of reliable early detection biomarkers, remains inadequate.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Surgery · 1994 · 121 citations · open access
Carcinoma of the Extrahepatic Bile Ducts The University of California at San Francisco Experience
AbstractOBJECTIVE: The authors investigated the combined experience of a single institution in treating bile duct carcinoma during the modern era. SUMMARY BACKGROUND DATA: Bile duct carcinomas are notoriously difficult to cure, with locoregional recurrence the rule, even after radical resection. Adjuvant efforts have included various radiation modalities, with limited success. Recently, charged-particle radiotherapy has also been used in these patients. METHODS: The authors performed a retrospective chart analysis of 129 patients with bile duct adenocarcinomas treated between 1977 and 1987 through the University of California at San Francisco, including 22 patients treated at Lawrence Berkeley Laboratory with the charged particles helium and neon. The minimum follow-up was 5 years. Survival, outcome, and complication results were analyzed. RESULTS: Sixty-two patients were treated with surgery alone (S), 45 patients received conventional adjuvant x-ray radiotherapy (S + X), and 22 were treated with charged particles (S + CP). The median survival times were 6.5, 11, and 14 months, respectively, for the entire group, and 16, 16, and 23 months in patients treated with curative intent. There was a survival difference in patients undergoing total resection compared with debulking (p = 0.05) and minor resections (p = 0.0001). Patients with microscopic residual disease had increased median survival times when they were treated with adjuvant irradiation, most markedly after CP (p = 0.0005) but also with conventional X (p = 0.0109). Patients with gross residual disease had a less marked but still statistically significant extended survival (p = 0.05 for S + X and p = 0.0423 for S + CP) after irradiatio CONCLUSIONS: The mainstay of bile duct carcinoma management was maximal surgical resection in these patients. Postoperative radiotherapy gave patients with positive microscopic margins a significant survival advantage and may be of value in selected patients with gross disease.
Differing rates of loss ofDPC4 expression and ofp53 overexpression among carcinomas of the proximal and distal bile ducts
AbstractBACKGROUND: Biliary tract carcinomas are clinically heterogeneous. It is not known if molecular heterogeneity underlies the clinical differences. METHODS: The authors evaluated 128 bile duct carcinomas, 88 of the distal common bile duct and 40 of more proximal origin (28 perihilar carcinomas, 12 intrahepatic carcinomas), immunohistochemically for abnormalities in the expression of the products of the DPC4 and p53 tumor-suppressor genes. Prognostic factors were evaluated in the series of distal bile duct carcinomas for which follow-up information was available. RESULTS: The authors found that a significantly higher percentage of distal bile duct carcinomas (55%) demonstrated loss of DPC4 expression than did the proximal bile duct carcinomas (15%; P < 0.001). They also found that a significantly higher percentage of the distal tumors abnormally expressed the p53 gene product (51% vs. 26%; P < 0.001). Among the distal common bile duct carcinomas, the presence of poorly differentiated histology correlated with decreased survival in multivariate analysis, while labeling for p53 or Dpc4, margin status, lymph node status, and tumor dimension did not correlate significantly with survival. CONCLUSIONS: These results demonstrate that abnormalities in DPC4 and p53 gene expression are frequent in distal common bile duct carcinomas, just as they are in pancreatic ductal adenocarcinoma, suggesting that these two tumor types might share a similar molecular pathogenesis. They also show that proximal and distal bile duct carcinomas have different patterns of inactivation of tumor-suppressor genes, indicating that they often arise through different molecular mechanisms likely reflecting their differing etiologies.
British Journal of Radiology · 2017 · 10 citations · open access
Salvage radiotherapy for locoregionally recurrent extrahepatic bile duct cancer after radical surgery
AbstractOBJECTIVE: This study evaluated the outcome of salvage radiotherapy for locoregionally recurrent extrahepatic bile duct cancer. METHODS: We performed a retrospective review of 23 extrahepatic bile duct cancer patients who underwent radiotherapy with or without concomitant chemotherapy for isolated locoregional recurrence after radical surgery between August 2001 and September 2013. The median disease-free interval was 11.8 months. Salvage radiotherapy was delivered to the recurrent tumour with or without initial operation bed up to a median dose of 54 Gy (range, 45-60). 18 patients received concomitant chemotherapy. RESULTS: The median follow-up period was 14.2 months for all patients, and 48.8 months for survivors. The median overall survival and progression-free survival (PFS) were 18.4 (range, 4.4-114.6) and 15.5 months (range, 1.6-114.6), respectively. On multivariate analysis, the use of concomitant chemotherapy was a favourable prognostic factor for PFS (p = 0.027), and prolonged disease-free interval (≥1 year) was associated with a significantly poor overall survival (p = 0.047). Grade 3 or higher toxicities did not occur in follow-up period. CONCLUSION: Salvage radiotherapy showed promising survival outcomes in locoregional recurrence of extrahepatic bile duct cancer. Our results indicated that concomitant chemotherapy was associated with improved PFS. Concurrent chemoradiotherapy can be a viable salvage treatment option in selected patients. Advances in knowledge: Locoregional recurrence is the most common pattern of failure after radical resection in extrahepatic bile duct cancer. In this study, salvage radiotherapy showed favourable survival outcomes without severe complications in locoregionally recurrent extrahepatic bile duct cancer patients.
Gastroenterology Research · 2009 · 4 citations · open access
Molecular Markers in the Pathogenesis of Cholangiocarcinoma: Potential for Early Detection and Selection of Appropriate Treatment
AbstractCholangiocarcinoma (CC) is a primary malignancy that arises from cholangiocytes, the epithelial cells lining the bile duct livers. The worldwide incidence of CC is increasing and despite of combined therapeutic strategies, its prognosis remains poor. Till now surgery remains the only curative treatment modality. Over the past years, several important studies have yielded new insights into the molecular mechanisms of cholangiocarcinoma. This review focused on critical molecular player during the development from inflammation and cellular and molecular pathogenesis of this disease. The novel prophylactic and therapeutic approach deals especially the molecules involved in inflammation of cholangiocite or those related to promotion and progression of CC. The elucidation of their specific effects and interaction of this complex mechanism will accelerate the development of new biomarker for early detection and predictor factors outcome in CC.
World Journal of Surgical Oncology · 2009 · 3 citations · open access
Isolated recurrence of distal adenocarcinoma of the extrahepatic bile duct on a draining sinus scar after curative resection: Case Report and review of the literature
AbstractBACKGROUND: Surgical resection remains the gold standard for the treatment of localized adenocarcinoma of the extrahepatic bile ducts. Yet, treatment of loco-regional recurrences is not well defined. CASE PRESENTATION: We present an unusual case of distal adenocarcinoma of the extrahepatic bile ducts that was treated with surgery and relapsed two years later with a solitary recurrence on the tract of a previous Redon drain. In addition, a review of the literature on management of loco regional relapses is presented. CONCLUSIONS: The ideal management of these patients still remains undefined. Decisions are made based on clinical parameters from retrospective series, such as tumor grade, surgical margins or lymph node involvement. Prospective studies, that include molecular and genetic markers, are needed to improve patient selection and outcomes on this population.
International Journal of Hepatobiliary and Pancreatic Diseases · 2017 · 0 citations · open access
Emerging therapies for the treatment of cholangiocarcinoma
AbstractCholangiocarcinoma (CCA) is a cancer arising from the epithelium of intrahepatic or extrahepatic bile ducts. Cholangiocarcinoma often has a poor prognosis due to late diagnosis and the incidence and mortality rate of intrahepatic CCA appear to be increasing. Current therapies include surgical resection, orthotopic liver transplantation, chemotherapy/chemoradiation and palliative care. Depending on the location, the 5-year survival for CCA ranges from 27–60%. Emerging new therapies are currently being developed for treating CCA include immunotherapy, altering the tumor microenvironment, targeting growth factor gene mutations and signal pathways and that control tumor growth, and targeting gene therapy. The objective of this paper is to summarize the research that is currently ongoing for treating this challenging disease.
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.
