DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for bile duct carcinoma — screening already-approved drugs against its 45-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 carcinoma maps to a 45-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 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
tripartite motif containing 24 (TRIM24) — TRIM24 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 benzyloxydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4YBM · 1.46 Å · ligand N-{6-[3-(benzyloxy)phenoxy]-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl}-3,4-dimethoxybenzenesulfonamide (4BJ). Experimental structure, not a prediction.
What the evidence adds up to
Of 151 patients with extrahepatic bile duct cancer who underwent surgical resection between 1986 and 1997, 49 (32.5%) survived five years or longer. The actual five-year survival rate was 47.8% after hepatobiliary resection (11 of 23), 28.0% after bile duct resection (7 of 25), and 30.1% after pancreatoduodenectomy (31 of 103). No five-year survivor existed among non-resected cases. Tumour histology and lymph node metastasis were independent prognostic factors. Seven long-term survivors had recurrent disease at five years, and recurrence was detected after five years in eight more patients. The actual cure rate was less than 19.2%, substantially lower than the five-year survival rate. None of the long-term survivors had a poorly differentiated tumour, though some had T3, lymph node metastasis, or microscopic margin involvement.
A separate review of 165 patients treated over thirty years at UCLA supported resection only for tumours that could be grossly removed at operation. For palliation, biliary-enteric bypass or operative intubation was preferred. The authors argued against palliative resection because of higher morbidity and mortality rates and poorer quality of life in surviving patients.
By 2024, immunotherapy combined with cisplatin and gemcitabine had been included in first-line treatment for bile duct carcinoma. Cholangiocarcinomas are genetically heterogeneous, and several targets have been identified for second-line therapy, including FGFR-2, NTRK, IDH-1, BRAF, and HER-2. A 2009 review noted that despite combined therapeutic strategies, prognosis remains poor, and surgery remains the only curative modality. That review called for elucidation of molecular mechanisms to develop biomarkers for early detection and predictors of outcome.
What is still missing are prospective trials that stratify patients by the genetic targets now identified, adequate funding to test these targeted and immunotherapy combinations in the adjuvant and advanced settings, and long-term follow-up protocols that extend beyond five years to capture late recurrences. The gap between five-year survival and actual cure remains unclosed.
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 · 2005 · 226 citations · open access
Actual Long-term Outcome of Extrahepatic Bile Duct Cancer After Surgical Resection
AbstractIn Brief Objectives: The objectives of this study were to analyze the actual long-term outcome after the surgical resection of extrahepatic bile duct cancer and to identify the characteristics shared by long-term survivors (5 years or longer). Summary Background Data: Although reported 5-year survival rates of extrahepatic bile duct cancer lie between 20% and 30%, these data are not reflecting the actual cure rate. Some patients survive longer than 5 years with recurrent disease. In some patients, recurrence is detected after 5 years. Accordingly, true cure rate is probably substantially lower than the 5-year survival rate. Methods: One hundred fifty-one patients from a total of 282 patients with extrahepatic bile duct cancer (excluding ampulla of Vater cancer) underwent surgical resection between 1986 and 1997. We analyzed the actual survival outcome and postresection prognostic factors after resection, which included hepatobiliary resection (HBR; extended either right or left hepatectomy, caudate lobectomy, and hilar bile duct resection, n = 23), bile duct resection (BDR; n = 25), and pancreatoduodenectomy (PD; n = 103). We also compared the clinicopathologic characteristics of actual long-term survivors (n = 49) with those who survived longer than 5 years and with short-term (<5 years) survivors. Results: Forty-nine of the 151 resection cases (32.5%) survived 5 years or longer; there was no 5-year survivor in the nonresected cases. The actual 5-year survival rate was 47.8% after HBR (11 of 23), 28.0% after BDR (7 of 25), and 30.1% after PD (31 of 103) (P = 0.083). Tumor histology and lymph node metastasis were identified as independent prognostic factors by multivariate analysis. Some long-term survivors had poor postoperative prognostic factors such as T3, lymph node metastasis, or microscopic margin involvement, but none with a poorly differentiated tumor. Seven long-term survivors had recurrent disease at 5 years, and recurrence was detected after 5 years in 8 more patients. Therefore, the actual cure rate (<19.2%) was substantially less than the 5-year survival rate. Conclusions: In cases of extrahepatic bile duct cancer, resection should be considered and efforts should be made to obtain a tumor-free margin. An aggressive surgical approach will give some survival benefit to the patients with even advanced disease. Long-term follow up is needed before declaring “a cure,” because late recurrence after 5 years is detected not infrequently. Adjuvant therapy, local and systemic, needs to be further developed. The authors present the experiences of a single institution on the topic of extrahepatic bile duct cancer in an effort to better define the natural history of this disease and to identify those factors affecting long-term survival. Some long-term survivors were found to have risk factors associated with a poor prognosis such as lymph node metastasis or margin involvement. The authors suggest that long-term follow ups of more than 5 years are requisite for determining cure in patients with bile duct cancer and that surgical resection should be actively applied in those with advanced disease.
AbstractAbstract Over the past 30 years, a total of 165 patients with bile duct cancer have been studied at the University of California at Los Angeles (UCLA), U.S.A. A review of careful retrospective analyses of surgical treatment is presented. The data support a treatment strategy of resection of those tumors which can be grossly removed at operation. Palliation of other patients is best done by biliary‐enteric bypass or operative intubation. The higher morbidity and mortality rates for palliative resections, together with a poorer quality of life in those patients surviving this procedure, argue against resection for palliative purposes .
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.
memo - Magazine of European Medical Oncology · 2024 · 1 citations · open access
Innovative therapeutic concepts for biliary tumors
AbstractSummary In recent years there have been significant changes in the treatment of bile duct carcinoma. Immunotherapy has been included in first-line treatment for about a year now (IO + cisplatin/gemcitabine). Cholangiocarcinomas are genetically very heterogeneous and several new targets have been identified in recent years. These play an important role, especially in second-line treatment. This review aims to highlight the key milestones of current treatment with a focus on targeted therapy options. Especially, current data on therapeutic options such as FGFR‑2, NTRK, IDH‑1, BRAF, HER‑2 are reported.
Progress of radiotherapy for hilar cholangiocarcinoma
AbstractThe rate of complete surgical resection is still low in hilar cholangiocarcinoma,which greatly affects the curative effect.Radiotherapy,one kind of treatment for tumors,has not been widely adopted in the past years.In recent years,with the development of radiotherapy technology,research of treating hilar cholangiocarcinoma through radiotherapy has become a spot.Many studies have shown that radiotherapy,as an adjuvant therapy for surgery and non-surgical treatment,can be the major means for treatment,and it could bring benefit for patients' survival extension and improvement of life quality.
Key words:
Bile duct neoplasms; Radiotherapy; Prognosis
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.
