DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for intrahepatic bile duct cancer — screening already-approved drugs against its 11-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleIntrahepatic bile duct cancer maps to a 11-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 intrahepatic 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
RAB28, member RAS oncogene family (RAB28) — RAB28 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 g3ddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2HXS · 1.1 Å · ligand GUANOSINE-3'-MONOPHOSPHATE-5'-DIPHOSPHATE (G3D). 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 (helium or neon). Among patients treated with curative intent, median survival was 16 months for surgery alone and for surgery plus conventional x-ray, and 23 months for surgery plus charged particles. Patients with microscopic residual disease had increased median survival after adjuvant irradiation, most markedly after charged particles (p = 0.0005) but also with conventional x-ray (p = 0.0109). A later retrospective study of 23 patients with locoregionally recurrent extrahepatic bile duct cancer after radical surgery reported a median overall survival of 18.4 months and median progression-free survival of 15.5 months after salvage radiotherapy (median dose 54 Gy); 18 patients received concomitant chemotherapy. On multivariate analysis, concomitant chemotherapy was a favourable prognostic factor for progression-free survival (p = 0.027). No grade 3 or higher toxicities occurred.
A 2017 review states that the benefit of adding neoadjuvant or adjuvant chemotherapy and/or radiotherapy to surgery for intrahepatic cholangiocarcinoma has not been shown to significantly improve prognosis, and that the role of radiotherapy in intrahepatic cholangiocarcinoma remains debated. A 2020 review notes that patients are often diagnosed at an advanced stage when the lesion cannot be resected, leading to limited systemic chemotherapy, and that molecular targeted therapy is an area of active investigation. A 2021 study reports that the protein EMI2 is overexpressed in cholangiocarcinoma cell lines and that silencing EMI2 inhibited proliferation, invasion, and migration, arrested cell cycle in G1 phase, and promoted apoptosis in vitro; the transcription factor YY1 was shown to bind the EMI2 promoter, and key proteins in the PI3K/Akt signalling pathway decreased after EMI2 silencing. A 2022 review catalogues genetic mutations that differ by tumour location (FGFR2 in intrahepatic; PRKACA, PRKACB, KRAS, TP53, ARID1A in extrahepatic) and notes that epigenetic features such as TP53 mutation with hypermethylation of p14ARF, DAPK, and/or ASC correlate with more aggressive disease.
What is missing is prospective randomised evidence for radiotherapy in intrahepatic cholangiocarcinoma, any validated molecular target that has led to an approved therapy for this specific disease, and a trial design that stratifies patients by the genetic and epigenetic markers now catalogued. The charged-particle data are from a single institution over a decade ending in 1987, with no modern replication. The salvage radiotherapy series is small and retrospective. No drug is mentioned in any of these abstracts that has been tested in a controlled trial for intrahepatic bile duct cancer and shown to improve survival.
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.
Radiotherapy of high bile duct carcinoma using intracatheter iridium 192 wire
AbstractThe authors developed an original procedure of endo-curietherapy of high bile duct carcinoma. An iridium 192 wire is inserted into either a percutaneous transhepatic catheter or a surgically implanted external diversion catheter. The delivered dose varies between 10 and 60 Gy at 1 cm from the wire. Four of the seven patients analyzed also received external irradiation. There were no systemic or local complications. All patients experienced symptomatic relief and four are alive with no evidence of disease. This well-tolerated procedure permits symptomatic palliation without excessive side effects for the patient. In some cases, a curative effect can be expected.
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.
Journal of Medical Case Reports · 2016 · 10 citations · open access
Common bile duct villous adenoma: a case report and review of the literature
AbstractBACKGROUND: According to the literature, benign bile duct tumors are exceedingly uncommon. To the best of our knowledge, we report the largest extrahepatic bile duct villous adenoma described in the literature. CASE PRESENTATION: We present a case of a 77-year-old Caucasian woman with obstructive jaundice. Laboratory tests revealed that she had elevated bilirubin and liver enzyme levels. A computed tomographic scan showed a homogeneous 5 × 3-cm mass obstructing the common bile duct. The results of brush cytology were consistent with a bile duct villous papilloma. However, on the basis of the tumor's radiological features, a preliminary diagnosis of extrahepatic bile duct malignant tumor was made. After discussion among the multidisciplinary team, a surgical resection of the bile duct tumor was performed. Histopathological examination confirmed a villous adenoma. The patient's postoperative course was uneventful. CONCLUSIONS: In patients with bulky extrahepatic bile duct tumors, surgical resection alone may be safe and curative.
Precise treatment of intrahepatic cholangiocarcinoma
AbstractAlthough surgical resection is currently recognized as the only effective treatment for intrahepatic cholangiocarcinoma (ICC), it is extremely difficult to diagnose because there are no obvious clinical symptoms at the early stage. Patients are often diagnosed at the advanced stage and the lesion cannot be resected which leads to limited systemic chemotherapy. So the mortality is still high. Accurate treatment is a hot topic in the medical field, and more and more attentions have been paid to enhance the treatments of patients. This article reviewed the issues related to surgical treatment, chemotherapy, molecular targeted therapy, and immunotherapy in patients with ICC, and focuses on the latest progress of molecular targeted therapy.
Key words:
Bile duct neoplasms; Intrahepatic cholangiocarcinoma; Precise treatment; Molecular targeted therapy
International Journal of Radiology & Radiation Therapy · 2017 · 0 citations · open access
Is there any Role of Radiotherapy in Intrahepatic Cholangiocarcinomas?
AbstractCholangiocarcinoma or bile duct cancer is a rare type of cancer which is prevalent in developed countries and its prevalence is increasing in developing countries. Cholangiocarcinoma is included in the list of lethal cancer. While surgery is the cornerstone of its management, the benefit of adding neoadjuvant or adjuvant treatment in the form of chemotherapy and/or radiotherapy have not been shown to significantly improving the prognosis of the patients. The role of radiotherapy in the management of intrahepatic cholangiocarcinoma remains debated. These cancers usually present at advanced stages and are associated with low rates of local control and overall survival. The indications and implications of radiotherapy in these carcinomas are still not very clear. However, planning target volume and biologically effective dose of radiation have a prognostic value and initial treatment response is helpful in predicting survival time. In this review, we tried to explore various ways and options where radiotherapy can provide some better results in treating resectable and unresectable IHCC.
YY1 activates EMI2 and promotes the progression of cholangiocarcinoma through the PI3K/Akt signaling axis
AbstractAbstract Background Cholangiocarcinoma (CCA) is one of the deadliest cancers of the digestive tract. The prognosis of CCA is poor and the 5-year survival rate is low. Bioinformatic analysis showed that early mitotic inhibitor 2 (EMI2) was overexpressed in CCA but the underlying mechanism is not known. Methods The data on bile duct carcinoma from TCGA and GEO databases were used to detect the expression of EMI2. The transcription factors of EMI2 were predicted using JASPAR and PROMO databases. Among the predicted transcription factors, YY1 has been rarely reported in cholangiocarcinoma, and was verified using the luciferase reporter gene assay. RT-PCR was performed to predict the downstream pathway of EMI2, and PI3K/Akt was suspected to be associated with it. Subsequently, in vivo and in vitro experiments were conducted to verify the effects of silencing and overexpressing EMI2 and YY1 on the proliferation, invasion, and metastasis of the bile duct cancer cells. Results EMI2 was highly expressed in CCA. Silencing EMI2 inhibited the proliferation, invasion, and migration of CCA cells, arrested cell cycle in the G1 phase, and promoted of apoptosis. The luciferase reporter gene assay showed that YY1 bound to the promoter region of EMI2, and after silencing YY1, the expression of EMI2 decreased and the progression of CCA was inhibited. Moreover, key proteins in the PI3K/Akt signaling pathway decreased after silencing EMI2. Conclusion EMI2 may be one of the direct targets of YY1 and promotes the progression of CCA through the PI3K/Akt signaling pathway.
Journal of Modern Oncology · 2022 · 0 citations · open access
The role of molecular genetic factors in the development of cholangiocellular cancer: A review
AbstractThis article highlights the main inducers of cholangiocarcinogenesis. Data are presented on the study of gene mutations, the variations of which depending on the localization of biliary cancer may be different (FGFR2 in intrahepatic PRKACA, PRKACB cholangiocarcinoma in extrahepatic cholangiocarcinoma). Mutations in the KRAS, TP53, ARIAD1A genes are common in extrahepatic bile duct cancer. Epigenetic events such as DNA hypermethylation, histone modifications, chromatin remodeling, and disturbances in miRNA expression are considered. A number of epigenetic features, such as the presence of a TP53 gene mutation with hypermethylation of p14ARF, DAPK, and/or ASC, correlate with a more aggressive course of the disease. The role of the SOX17 gene in the development of drug resistance is highlighted. The study of molecular genetic features of extrahepatic bile duct cancer is an important aspect in understanding the pathogenesis of this type of tumor, reveals new prognostic and diagnostic markers of the disease. It is possible that in the future, as knowledge is accumulated, this will make it possible to individualize approaches to the treatment of this category of patients.
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.
