DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for bile duct papillary neoplasm — screening already-approved drugs against its 21-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 papillary neoplasm maps to a 21-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 papillary neoplasm 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
KRas proto-oncogene, GTPase (KRAS) — KRAS 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 gnpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7VVB · 1.7 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER (GNP). Experimental structure, not a prediction.
What the evidence adds up to
Twenty-five patients with intraductal papillary neoplasm of the bile ducts underwent surgery between 1995 and 2006. Five of those lesions were found incidentally. On imaging, 23 of the 25 showed bile duct dilatation, with or without an intraductal mass or cystic changes. Twenty-three patients had hepatic resection, with or without extrahepatic bile duct resection. No in-hospital deaths occurred. Median survival for resected patients was 59.8 months; 1-, 2-, and 4-year survival rates were 90.5%, 84.0%, and 84.0%. All six patients with benign IPN-B were alive at a mean of 26.2 postoperative months without recurrence. The authors concluded that aggressive surgical resection is the treatment of choice and that prognosis for benign IPN-B is excellent.
A 2022 commentary notes that intraductal papillary neoplasm of the bile duct is a precursor of invasive cholangiocarcinoma, that early identification may improve the poor prognosis, but that classical imaging often fails to make the diagnosis. It states that cholangioscopy may contribute to the diagnostic work-up and that precise pre-operative evaluation is necessary because surgery is the therapy of choice. No new patient data or survival figures are provided in that commentary.
A 2011 study of a partially covered nitinol stent for palliative treatment of malignant bile duct obstruction included 70 patients (mean age 69) across seven centres. The obstruction was due to pancreatic cancer in 68.1% and was located in the distal common bile duct in 66.7%. Technical success was 97%; clinical success at a median follow-up of 144 days was 94% (62 of 66). Re-obstruction occurred in four patients (two migrations, two obstructions) at a mean of 110 days, and all four were managed endoscopically. Acute cholecystitis occurred in three patients (4.5%), acute pancreatitis in one (1.5%). The authors concluded that the stent was easy to use, safe, and effective, but that its biliary patency did not appear superior to that of covered Elgiloy stents. They noted that the choice between covered and uncovered self-expanding metal stents for malignant distal bile duct obstruction remains empirical and that further prospective randomised studies are needed.
What is still missing are prospective randomised trials comparing covered and uncovered metal stents for malignant bile duct obstruction, and any trial data on drug therapy for intraductal papillary neoplasm of the bile duct. No drug treatment was tested or mentioned in any of these abstracts. Patient stratification by histologic subtype or molecular markers was not addressed. The 2008 surgical series is small and retrospective, and the 2022 commentary offers no new evidence.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Surgical Oncology · 2008 · 80 citations
Intraductal papillary neoplasm of the bile ducts: The clinical features and surgical outcome of 25 cases
AbstractBACKGROUND AND OBJECTIVES: Intraductal papillary neoplasm of the bile ducts (IPN-B) is considered an uncommon tumor. The purpose of this study was to evaluate the clinical, radiological, and histopathological characteristics of IPN-B, and its prognosis. METHODS: From October 1995 to August 2006, a retrospective analysis was made of 25 patients that underwent surgery for IPN-B. Clinical features and radiological, pathological, and operative findings were reviewed, and survival rates were determined. RESULTS: In five patients (20.0%), lesions were incidentally found. Radiologically, 23 of the 25 (92.0%) showed bile duct dilatation, bile duct dilatation with or without an intraductal mass, and cystic changes of bile ducts. Twenty three of the 25 patients underwent hepatic resection with or without extrahepatic bile duct resection. No in hospital mortality occurred. Median survival time of resected patients was 59.8 months and 1-, 2-, and 4-year survival rates were 90.5%, 84.0%, and 84.0%, respectively. All six patients with benign IPN-B remained alive at a mean of 26.2 postoperative months without recurrence. CONCLUSIONS: A diagnosis of IPN-B is usually made in patients with biliary dilatation by radiologic study. The prognosis of IPN-B, especially of the benign category, is excellent. Aggressive surgical resection is the treatment of choice for IPN-B.
The added value of peroral cholangioscopy to diagnose intraductal papillary neoplasm of the bile duct
AbstractIntraductal papillary neoplasm of the bile duct is a precursor of invasive cholangiocarcinoma [1]. Early identification and intervention may improve the poor prognosis of this disease, but diagnosis by classical imaging is often difficult [2]. Also, as surgery is the therapy of choice, a precise pre-operative evaluation is necessary [3] [4]. Cholangioscopy may contribute to the diagnostic work-up.
Commentaire de travail de G. Costamagna et al., pp. 317
AbstractSee also: A new partially covered nitinol stent for palliative treatment of malignant bile duct obstruction: a multicenter single-arm prospective study Endoscopy 2011; 43(04): 317-324 DOI: 10.1055/s-0030-1256294 G. Costamagna, A. Tringali, D. N. Reddy, J. Devière, M. Bruno, T. Ponchon, H. Neuhaus, M. Mutignani, G. V. Rao, S. Lakhtakia, O. Le Moine, P. Fockens, E. A. J. Rauws, V. Lepilliez, B. Schumacher, A. Seelhoff, D. Carr-Locke. Une nouvelle prothèse biliaire en nitinol partiellement couverte pour le traitement palliatif des sténoses biliaires malignes. Etude prospective multicentrique à un seul bras Dans le traitement palliatif des sténoses malignes de la voie biliaire principale, la perméabilité des prothèses métalliques auto expansibles (PMAE) non couvertes peut être compromise par la prolifération tumorale à travers les mailles. De ce fait des modèles de PMAE couvertes en acier ou alliage Elgiloy ont été développées. Leur rigidité relativement élevée pu être considérée comme responsable d'impaction de leur pôle proximal au niveau de la paroi en cas d'angulation importante de la voie biliaire principale incitant à l'utilisation de PMAE plus souples en Nitinol. Dans ce travail, 70 patients (âge moyen 69 ans) étaient inclus dans 7 centres (Europe 5, Inde 1, USA 1). L'objectif principal était de déterminer la durée de drainage efficace d'une nouvelle PMAE en Platinol (mailles en platine recouvert de Nitinol) partiellement couverte par un polymère de silicone (Wallflex® Boston Scientific) pour le traitement palliatif de sténoses malignes de la voie biliaire principale. La mise en place était réalisée sur un fil guide de 0,035 pouces selon la technique “Rapid Exchange”. La sténose était liée à un cancer du pancréas chez 68,1 % des patients, elle était localisée au niveau de la voie biliaire principale distale dans 66,7 % Le succès technique était de 97%, un échec était lié au non franchissement de la sténose par le fil guide. La PMAE était mise en place dans 44,9 % en remplacement d'une prothèse plastique et dans 49,3% une sphinctérotomie avait été pratiquée lors d'une procédure précédente. Le succès clinique à l'issu d'un suivi médian de 144 jours [5–225], jugé sur l'efficacité du traitement de l'obstruction biliaire était de 94 % (62/66). Une ré-obstruction biliaire survenait chez 4 patients (2 migrations et 2 obstructions) dans un délai moyen de 110 jours. Un retraitement endoscopique était efficace pour les 4. Depuis une décennie en raison d'une durée de perméabilité plus longue par rapport aux prothèses en plastique, les prothèses métalliques auto expansibles (PMAE) constituent le traitement de référence des sténoses malignes de la VBP. La durée de perméabilité semble être supérieure pour les PMAE couvertes, avec une durée de survie des patients similaire. Les avantages théoriques de l'utilisation d'une PMAE couverte sont d'éviter la prolifération tumorale et également de permettre l'extraction de la prothèse si une option chirurgicale était retenue secondairement. Une PMAE couverte est susceptible de couvrir la convergence cystico-biliaire sachant qu'aucune étude prospective randomisée n'a montré un risque supérieur de cholécystite avec les PMAE couvertes versus non couverte. Dans ce travail, les auteurs précisent que pour un patient la PMAE était facilement mobilisée pour être positionnée sous la convergence cystico biliaire dans le but de prévenir une complication vésiculaire. Trois cholécystites aiguës étaient rapportées (4,5 %), ce qui est conforme aux valeurs retrouvée dans les travaux précédents (2,5–10 %). Un risque de migration supérieur pour les PMAE couverte a été documenté. Il s'est produit pour deux patients (3%) dans ce travail. Une seule pancréatite aiguë (1,5 %) est survenue alors que cette complication est habituellement plus fréquente avec les PMAE couvertes. Cependant une sphinctérotomie avait été pratiquée lors d'une CPRE antérieure dans la moitié des cas. Les auteurs concluent à une utilisation aisée, sûre et efficace de ce modèle de PMAE en nitinol partiellement couverte. Les performances sur la perméabilité biliaire ne semblent pas supérieures à celles qui étaient obtenues avec les PMAE couvertes en Elgiloy mais néanmoins dans notre pratique les PMAE en nitinol couvertes apparaissent subjectivement d'un maniement plus aisé que les modèles en acier ou alliage. Actuellement, en l'absence d'arguments de niveau de preuve suffisant, dans les sténoses malignes de la VBP le choix entre une PMAE non couverte ou une PMAE couverte est encore empirique nécessitant de poursuivre les études prospectives randomisées. Une étude sous l'égide de la sfed est en cours.
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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