DeCure for Pancreatic intraductal papillary-mucinous neoplasm
DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for pancreatic intraductal papillary-mucinous neoplasm — screening already-approved drugs against its 6-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePancreatic intraductal papillary-mucinous neoplasm maps to a 6-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 pancreatic intraductal papillary-mucinous 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
Between 1987 and 2000 at Johns Hopkins Hospital, 60 patients underwent pancreatic resection for intraductal papillary mucinous neoplasms (IPMNs). Mean age at presentation was 67.4 years. 37% of patients had an IPMN with an associated infiltrating adenocarcinoma. The 5-year survival rate for all 60 patients was 57%. In a subset of 50 IPMNs stained for the Dpc4 protein, all intraductal or noninvasive components strongly expressed Dpc4, while 84% of associated infiltrating cancers expressed it. The authors concluded that IPMNs are clinically, histologically, and genetically distinct from pancreatic ductal adenocarcinomas.
A later cohort study of 203 patients who underwent partial pancreatic resection for an IPMN found that after a median follow-up of 40 months, new lesions appeared in the pancreatic remnant in 17 patients (8%). The median interval from initial resection to detection of a new lesion was 38 months. Only 1 of those 17 patients had a positive surgical margin at the time of initial resection. Among the 17 patients with new lesions, 12 had side-branch disease detected only by imaging and received no treatment; 5 underwent further surgery, including 2 with invasive ductal carcinoma (1 of whom had liver metastases). The authors noted that as follow-up time increases, new lesions will likely appear regardless of whether the initial surgical margin was negative.
A 2014 review of the molecular pathology of IPMNs stated that a large number of genes acting as oncogenes or tumour suppressor genes have been identified in pancreatic juice, blood, or resection samples. However, the review concluded that further research is required before these molecular findings can be used clinically to distinguish aggressive IPMNs requiring surgery from benign ones that could be observed. What remains missing is a validated molecular test that can stratify patients by malignant potential without requiring resection, as well as prospective trials testing whether such stratification improves outcomes. The natural history of untreated low-risk IPMNs also remains poorly defined, and no drug therapy is mentioned in any of these abstracts.
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 · 2001 · 312 citations · open access
Intraductal Papillary Mucinous Neoplasms of the Pancreas: An Increasingly Recognized Clinicopathologic Entity
AbstractOBJECTIVE: To assess the authors' experience with intraductal papillary mucinous neoplasms of the pancreas (IPMNs). SUMMARY BACKGROUND DATA: Intraductal papillary mucinous neoplasms of the pancreas are being recognized with increasing frequency. METHODS: All patients who underwent pancreatic resection for an IPMN at the Johns Hopkins Hospital between January 1987 and December 2000 were studied. The data were compared with those of 702 concurrent patients with infiltrating ductal adenocarcinoma of the pancreas not associated with an IPMN resected by pancreaticoduodenectomy. RESULTS: In the 13-year time period, 60 patients underwent pancreatic resection for IPMNs, with 40 patients undergoing resection in the past 3 years. Mean age at presentation was 67.4 +/- 1.4 years. The most common presenting symptom in patients with IPMNs was abdominal pain (59%). Most IPMNs were in the head of the pancreas or diffusely involved the gland, with 70% being resected via pancreaticoduodenectomy, 22% via total pancreatectomy, and 8% via distal pancreatectomy. Twenty-two patients (37%) had IPMNs with an associated infiltrating adenocarcinoma. In a subset of IPMNs immunohistochemically stained for the Dpc4 protein (n = 50), all of the intraductal or noninvasive components strongly expressed Dpc4, whereas 84% of associated infiltrating cancers expressed Dpc4. The 5-year survival rate for all patients with IPMNs (n = 60) was 57%. CONCLUSION: Intraductal papillary mucinous neoplasms represent a distinct clinicopathologic entity being recognized with increasing frequency. IPMNs are clinically, histologically, and genetically disparate from pancreatic ductal adenocarcinomas. The distinct clinical features, the presumably long in situ or noninvasive phase, and the good long-term survival of patients with IPMNs offer a unique opportunity for early diagnosis, curative resection, and further studies of the molecular genetics and natural history of these unusual neoplasms.
Fate of the Pancreatic Remnant After Resection for an Intraductal Papillary Mucinous Neoplasm
AbstractOBJECTIVE: To determine the occurrence of new disease in the pancreatic remnant after resection for intraductal papillary mucinous neoplasms. DESIGN: A longitudinal level II cohort study. SETTING: Virginia Mason Medical Center, Seattle, Washington. PATIENTS: The primary cohort was a "resection cohort" of 203 patients who underwent partial pancreatic resection for an intraductal papillary mucinous neoplasm. MAIN OUTCOME MEASURES: The occurrence rate of lesions in the pancreatic remnant after resection for an intraductal papillary mucinous neoplasm, determined by use of an annual computed tomographic scan of the pancreas. RESULTS: New lesions were observed in the remnant of 17 of the 203 patients (8%) after a median follow-up of 40 months and a median interval of 38 months from the initial resection. Only 1 of these 17 patients with new lesions had a surgical margin that was positive for an adenoma at the time of resection. Comparing the 17 patients with new lesions with the 186 patients without new lesions, we found no difference in age, sex, procedure type, location in ductal system, original histology, or original margin status. In the new lesion group, no treatment was used for 12 patients who had side-branch disease detected by imaging (6% of all patients). Surgical treatment was used for 5 patients (2% of all patients): 2 with adenomas, 1 with a carcinoma in situ, and 2 with an invasive ductal carcinoma (1 with liver metastases). CONCLUSIONS: We found that, following a partial pancreatic resection for an intraductal papillary mucinous neoplasm and a 40-month follow-up with an annual computed tomographic scan of the pancreas, 17 of 203 patients (8%) developed a new intraductal papillary mucinous neoplastic lesion in the pancreatic remnant. As follow-up time increases, we suspect that new lesions will constantly appear regardless of whether the surgical margin was negative at initial resection.
World Journal of Gastroenterology · 2014 · 30 citations · open access
Molecular pathology of intraductal papillary mucinous neoplasms of the pancreas
AbstractSince the first description of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas in the eighties, their identification has dramatically increased in the last decades, hand to hand with the improvements in diagnostic imaging and sampling techniques for the study of pancreatic diseases. However, the heterogeneity of IPMNs and their malignant potential make difficult the management of these lesions. The objective of this review is to identify the molecular characteristics of IPMNs in order to recognize potential markers for the discrimination of more aggressive IPMNs requiring surgical resection from benign IPMNs that could be observed. We briefly summarize recent research findings on the genetics and epigenetics of intraductal papillary mucinous neoplasms, identifying some genes, molecular mechanisms and cellular signaling pathways correlated to the pathogenesis of IPMNs and their progression to malignancy. The knowledge of molecular biology of IPMNs has impressively developed over the last few years. A great amount of genes functioning as oncogenes or tumor suppressor genes have been identified, in pancreatic juice or in blood or in the samples from the pancreatic resections, but further researches are required to use these informations for clinical intent, in order to better define the natural history of these diseases and to improve their management.
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.
