DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for extrahepatic bile duct carcinoma — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleExtrahepatic bile duct carcinoma maps to a 1-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 extrahepatic 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
solute carrier family 30 member 10 (SLC30A10) — SLC30A10 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9KVX · 2.79 Å · ligand none (apo structure). 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 came from the non-resected group. 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. No patient with a poorly differentiated tumour was among the long-term survivors.
A phase I/II study of radiochemotherapy enrolled 11 patients with histologically confirmed adenocarcinoma of the distal or hilar extrahepatic bile ducts after non-curative operations (R1/R2 resection or surgical exploration). Treatment consisted of fractionated radiotherapy (40 Gy plus 9.6 Gy boost) with weekly gemcitabine 100 mg/m², followed by gemcitabine 1000 mg/m² and capecitabine 1500 mg/m². Grade 3/4 toxicity occurred in 7 patients, including leucopenia, thrombopenia, nausea, a bleeding ulcer, and cachexia. Of 8 patients with measurable disease, one had a complete response, one a partial response, and three had stable disease for at least three months. Median actuarial survival was 296 days.
A 2023 review states that upfront surgery with adjuvant capecitabine is the standard of care for early-stage hilar cholangiocarcinoma and the only curative therapy. Most patients present with locally advanced or metastatic disease and rely on systemic therapy, but survival remains poor. For intrahepatic cholangiocarcinoma, a 2016 review notes that gemcitabine and cisplatin is the systemic therapy practice standard for non-resectable disease, and that neoadjuvant therapy with liver transplantation may be a new option.
What is still missing are adequately powered randomised trials of adjuvant and neoadjuvant regimens specifically for extrahepatic bile duct carcinoma, reliable biomarkers to stratify patients by likelihood of benefit from aggressive surgery or radiochemotherapy, and funding for multi-centre studies that can move beyond single-institution case series and small phase I/II cohorts.
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.
Multi-Disciplinary Care of Hilar Cholangiocarcinoma: Review of Guidelines and Recent Advancements
AbstractCholangiocarcinoma (CCA) is a rare malignancy of the intrahepatic and extrahepatic biliary ducts. CCA is primarily defined by its anatomic location: intrahepatic cholangiocarcinoma versus extrahepatic cholangiocarcinoma. Hilar cholangiocarcinoma (HC) is a subtype of extrahepatic cholangiocarcinoma that arises from the common hepatic bile duct and can extend to the right and/or left hepatic bile ducts. Upfront surgery with adjuvant capecitabine is the standard of care for patients who present with early disease and the only curative therapy. Unfortunately, most patients present with locally advanced or metastatic disease and must rely on systemic therapy as their primary treatment. However, even with current systemic therapy, survival is still poor. As such, research is focused on developing targeted therapies and multimodal strategies to improve overall prognosis. This review discusses the work-up and management of HC focused on the most up-to-date literature and ongoing clinical trials.
A phase I/II study of radiochemotherapy in extrahepatic bile duct carcinoma
Abstract4233 Background: The 5-year survival rate of patients with curatively resected extrahepatic bile duct carcinoma is less than 25%. Despite the poor prognosis there is a lack of adjuvant therapies. Phase II trials demonstrated that advanced extrahepatic bile duct carcinomas respond to both chemotherapy with gemcitabine and radiotherapy. Our objective was to define a feasible and effective radiochemotherapy in bile duct cancer. Methods: Patients with histologically confirmed adenocarcinoma of the distal or hilar extrahepatic bile ducts were prospectively enrolled after non-curative operations (R1/R2-resection or surgical exploration). Treatment consisted of a fractionated radiotherapy with 40 Gy + 9.6 Gy Boost accompanied by gemcitabine 100 mg/m2 weekly x 5. After a two week rest gemcitabine (1000 mg/m2 IV weekly x 2 q3w) and capecitabine (1500 mg/m2 PO D1–14 q3w) were given. Treatment continued for 6 cycles in nonmeasurable disease or until disease progression or intolerable toxicity. Primary endpoint was toxicity; secondary endpoints were response rate in measurable disease and overall survival. Results: 11 Patients (hilar/distal carcinoma: 8/3) were enrolled. Radiotherapy was completed in all patients and a total of 49 cycles of chemotherapy were applied. Grade 3/4 toxicity was observed in 7 patients and consisted of leucopenia (2 cycles), thrombopenia (1), nausea (3), a bleeding ulcer (1) and cachexia in 3 patients. The most frequent mild toxicities were asthenia and nausea in 50% and 40% of cycles, respectively. Therapy was discontinued in 2 patients. Of 8 patients with measurable disease, one each had a complete and a partial response and 3 had stable disease for at least 3 months. Median actuarial survival is 296 days. Conclusions: Radiochemotherapy with gemcitabine followed by gemcitabine and capecitabine is an active regimen with manageable toxicity in postoperative palliative treatment of extrahepatic bile duct cancer. No significant financial relationships to disclose.
Treatment progress of intrahepatic cholangiocarcinoma
AbstractSurgical resection is still the mainstay for treatment of intrahepatic cholangiocarcinoma (ICC). Gemcitabine and cisplatin is a systemic therapy practice standard for patients with non-resectable ICC. Neoadjuvant therapy with liver transplantation may be a new therapeutic option for patients with ICC. In addition, radiotherapy, hepatic intra-arterial therapy, ablation therapy and molecular targeted therapy are important components of comprehensive therapy for ICC.
Key words:
Bile ducts, intrahepatic; Bile duct neoplasms; Therapeutics; 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.
