DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for pancreatic adenocarcinoma — screening already-approved drugs against its 44-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePancreatic adenocarcinoma maps to a 44-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
approvedDocetaxelApproved drug
Structures already discussed alongside pancreatic adenocarcinoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
TUBULIN ALPHA-BETA DIMER, ELECTRON DIFFRACTION — Docetaxel has a real, experimentally solved structure in complex with this target (PDB 1TUB, 3.7 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet txldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1TUB · 3.7 Å · ligand Docetaxel (TXL). Experimental structure, not a prediction.
What the evidence adds up to
Only about one in five patients present with tumours amenable to surgical resection, and even after apparently complete removal of a localised neoplasm long-term survival remains poor. Perioperative mortality for pancreaticoduodenectomy at major centres has fallen to roughly one percent, but surgery alone is rarely curative. The 2004 review notes that identifying effective adjuvant therapy is increasingly important as more centres become capable of performing the operation safely.
Gemcitabine-based chemotherapy has been the cornerstone of treatment for advanced pancreatic cancer since before 2008. Research into the molecular pathogenesis of the disease has revealed complex, heterogeneous signalling pathways and defined mutations. A 2008 review concludes that this molecular heterogeneity is a major reason why targeted therapies have failed in pancreatic adenocarcinoma. The same review suggests that targeting multiple oncogenic pathways simultaneously might improve survival, but no such regimen is described as having succeeded in the abstracts provided.
By 2015 the situation had not improved. An editorial states that pancreatic cancer is notoriously resistant not only to conventional cytotoxic therapies but also to almost all targeted agents developed to that point. The disease-related mortality nearly equals its incidence, making it one of the most challenging malignancies to treat. The editorial highlights recent preclinical and clinical research but does not report any breakthrough in targeted therapy for pancreatic adenocarcinoma.
What remains missing is a targeted therapy strategy that overcomes the molecular heterogeneity of the tumour. No abstract provides evidence that any specific targeted agent improves survival in a randomised trial. The field still lacks a validated method for stratifying patients by the dominant oncogenic pathway in their tumour, and the funding and trial designs needed to test combination regimens against that heterogeneity have not yet produced a positive result.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 2004 · 77 citations
Adjuvant Therapy for Pancreatic Cancer — The Debate Continues
AbstractSurgical therapy currently offers the only potential cure for pancreatic adenocarcinoma. Surgical morbidity and mortality have decreased dramatically in recent years; the perioperative mortality associated with pancreaticoduodenectomy in major centers is approximately 1 percent. However, only a few patients present with tumors that are amenable to resection, and even after resection of a seemingly localized neoplasm, long-term survival is poor.1 Since many medical centers now have the capacity to resect pancreatic cancer safely, it is increasingly important to identify effective postoperative (adjuvant) therapy if we are to achieve long-term success in treating this disease.The potential benefit of adjuvant therapy . . .
Expert Opinion on Therapeutic Targets · 2008 · 21 citations
Challenges in developing targeted therapy for pancreatic adenocarcinoma
AbstractBACKGROUND: Pancreatic adenocarcinoma is a leading cause of cancer deaths in the US. Gemcitabine-based chemotherapy remains the cornerstone treatment for advanced pancreatic cancers. Research into the molecular pathogenesis of pancreatic cancers has allowed scientists to understand the complex heterogeneous signals associated with them. Targeting these pathways with chemical inhibitors could improve patient outcome. OBJECTIVE: To describe the molecular heterogeneity typical of pancreatic cancers and to discuss targeted therapies in development, and the challenges facing these agents. METHODS: We reviewed Pub Med. literature, clinical trial database (clinicaltrials.gov), American Society of Clinical Oncology (ASCO) and American Association of Cancer Research (AACR) websites. CONCLUSIONS: Molecular pathogenesis of pancreatic cancer involves multiple pathways and defined mutations. This molecular heterogeneity is a major reason for failure of targeted therapy. Targeting multiple oncogenic pathways using novel targeted therapies could improve patient survival.
World Journal of Gastrointestinal Oncology · 2015 · 6 citations · open access
Targeted therapies for pancreatic adenocarcinoma: Where do we stand, how far can we go?
AbstractPancreatic adenocarcinoma (usually referred to as pancreatic cancer) is a highly lethal and aggressive malignancy with a disease-related mortality almost equaling its incidence, and one of the most challenging cancers to treat. The notorious resistance of pancreatic cancer not only to conventional cytotoxic therapies but also to almost all targeted agents developed to date, continues to puzzle the oncological community and represents one of the biggest hurdles to reducing the death toll from this ominous disease. This editorial highlights the most important recent advances in preclinical and clinical research, with regards to targeted therapeutics for pancreatic cancer, outlines current challenges and provides an overview of potential future perspectives in this rapidly evolving field.
Preoperative radiotherapy and docetaxel in resectable pancreatic adenocarcinoma: A phase II trial
Abstract4099 Background: We previously reported results a phase I trial of weekly docetaxel concurrently with radiation therapy in patients (pts) with locally advanced pancreatic adenocarcinoma (Pancreas, Vol 27, N°3, 2003). We prospectively explored this regimen in 34 pts with biopsy proven potentially resectable pancreatic adenocarcinoma. Methods: Treatment consisted of concomitant radiotherapy (45 Gy within 5 weeks directed at the pancreatic tumor and regional lymphatics) with 5 weekly doses of docetaxel (30 mg/m 2 /week) by 1-hour infusion, followed by a complete staging evaluation 3–4 weeks after chemo-radiation. Pts without disease progression underwent surgery. Results: From May, 2003 to July, 2005, this study enrolled 34 pts (59% men) with median age 62 years (range 45–72). Median tumor size was 3 cm. Pretreatment Endoscopic Ultrasound (EUS) staging was uT1 (7 pts), uT2 (25 pts), uT3 (2pts), uN0 (26 pts) and uN1 (8 pts). Median pretreatment CA 19.9 levels was 114 (range 1–9432). All pts (97%) but one completed radiation and 91% (31 pts) received the 5 weekly doses of docetaxel. Adverse events included grade 3/4 asthenia (28%), grade 3/4 nausea/vomiting (10%), grade 3/4 anemia (7%) and grade 3/4 neutropenia (7%). Median time between diagnosis and surgery was 3.7 months (range 2.8–8.7). Ten pts (29%) presented progressive disease after chemo-radiation and one additional patient (pt) voluntary stopped treatment procedure. Twenty three pts (68%) underwent surgical procedure, which was with curative intent in 17 pts (50%). One pt died within the 30-day post operative period. Pathological response was observed in 7 pts (30%), including 2 complete response. The median Disease Free Survival (DFS) was 11 months and the 2-year DFS was 21%. The median overall survival (OS) was 14 months. The 2-year DFS for the 17 pts resected with a curative intent was 50.4%. In this subgroup, median overall survival was not reached. Conclusions: Pre-operative combination of radiotherapy and docetaxel is feasible with tolerable toxicity and with promising pathological response. A randomized phase III study comparing this regimen (radiotherapy and docetaxel) and surgery versus surgery alone is starting. Supported in part by Sanofi Aventis, France. No significant financial relationships to disclose.
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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