DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for bile duct cancer — screening already-approved drugs against its 4-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 cancer maps to a 4-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 cancer 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
mutS homolog 2 (MSH2) — MSH2 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 adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8RB1 · 2.085 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
In a retrospective series of 129 patients treated between 1977 and 1987 at the University of California at San Francisco, median survival for surgery alone was 6.5 months, for surgery plus conventional adjuvant x-ray radiotherapy 11 months, and for surgery plus charged-particle radiotherapy 14 months. Among patients treated with curative intent, those figures were 16, 16, and 23 months. Patients with microscopic residual disease who received adjuvant irradiation had longer median survival, most markedly after charged particles (p = 0.0005) but also with conventional x-ray (p = 0.0109). For gross residual disease the survival extension 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.
An earlier review of 165 patients at UCLA from 1958 to 1988 supported resection of tumours that could be grossly removed. Palliation was best achieved by biliary-enteric bypass or operative intubation. The authors argued against palliative resection because of higher morbidity and mortality and poorer quality of life. In a separate series of 52 patients with hepatoportal bile duct cancer treated between 1991 and 1996, 17 received surgical resection (32.7%). One-year survival after resection was 71.4%, two-year 35.7%, three-year 10.4%; for drainage alone the corresponding rates were 30%, 16.8%, and 0% (p < 0.05). Mean survival was 21.1 months after curative resection and 7.5 months after non-curative resection (p < 0.05). Operative mortality was 6.0% for drainage and 5.9% for resection (p > 0.05).
A 2020 review of combined treatment for resectable common bile duct cancer reported that only capecitabine could be routinely prescribed postoperatively, with median survival 51 months versus 36 months in the control group (p = 0.028). Neoadjuvant chemotherapy for primary resectable tumours was described as still less studied and mostly negative; the authors stated it should not be applied outside research protocols. A regimen of gemcitabine, cisplatin and nab-paclitaxel showed a partial response rate of 45% in patients with unresectable biliary cancer. A retrospective study of neoadjuvant radiotherapy combined with gemcitabine reported a partial response in 70% of patients and a reliable improvement in recurrence-free (p = 0.0263) and overall (p = 0.00187) survival compared with no neoadjuvant therapy.
A 2024 review notes that immunotherapy plus cisplatin and gemcitabine has been included in first-line treatment for about a year, and that several new targets (FGFR-2, NTRK, IDH-1, BRAF, HER-2) have been identified, especially for second-line therapy. What remains missing are prospective randomised trials large enough to test these targeted and combination approaches against standard care, particularly in the neoadjuvant and adjuvant settings, and reliable biomarkers to stratify patients by genetic subtype.
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.
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 .
World Journal of Gastroenterology · 1999 · 7 citations · open access
Surgical resection for hepatoportal bile duct cancer
AbstractAIM:To discuss the effect of surgical procedures on the prognosis of patients of bile duct cancer and their indications.METHODS:A retrospective analysis was made for 52 cases of hepatoportal bile duct cancer treated from January 1991 to December 1996. All the cases were classified according to the modified Bismuth-Corlettle system and received appropriate operation. Therapeutic effects were evaluated on the basis of their survival rates,jaundice elimination, comfort index,operative mortality and complications.RESULTS:Seventeen cases received surgical resection (32.7%). The survival rate was 71.4%, 35.7% and 10.4% for one, two and three years respectively, and was 30%, 16.8% and 0% for those with drainage (P < 0.05).The mortality rate was 6.0% for the drainage group and 5.9% for the resection group (P > 0.05). Of the 17 resected patients,8 (47.1%) had curative resection and 9 (52.9%) noncurative resection. Their mean survival time was 21.1 months and 7.5 months respectively (P < 0.05).CONCLUSION:Proper surgical procedure should be used on the basis of the local and general conditions of the patients, and aggressive resection with or without liver resection is a valid procedure for the treatment of hepatoportal bile duct cancer and can significantly improve the prognosis of patients.
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.
Annaly khirurgicheskoy gepatologii = Annals of HPB surgery · 2020 · 0 citations · open access
Combined treatment options for resectable common bile duct cancer patients
AbstractThis article demonstrates a review of scientific works enlightened to combined treatment options for common bile duct cancer patients. The role of adjuvant therapy is highlighted. It has been shown that only capecitabine can be routinely prescribed in the postoperative period: median survival rate in general group of patients consisted 51 month versus 36 month in control group, ( p = 0.028). Neoadjuvant chemotherapy for common bile duct cancer patients is still less studied and the research works results are mostly negative. At present, preoperative chemotherapy for patients with primary resectable tumors should not be applied currently excepting the scientific research protocol boundaries. A new chemotherapy regimen including gemcitabine, cisplatine and nab-paclitaxel has appeared which demonstrates a partial response to therapy reaching 45% for the patients with unresectable biliary cancer. The data of the retrospective study showing the positive role of neoadjuvant radiotherapy combined with gemcitabine: 70% of patients had a partial response as well as reliable improvement of recurrence-free ( p = 0.0263) and overall ( p = 0.00187) survival rates was observed compared to the group of patients who had no neoadjuvant therapy. The necessity of search for new additional treatment options for the common bile duct cancer patients in preoperative and postoperative period leaves no doubt.
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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