DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for pancreatic ductal adenocarcinoma — screening already-approved drugs against its 45-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePancreatic ductal adenocarcinoma maps to a 45-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
approvedGemcitabineApproved drug
Structures already discussed alongside pancreatic ductal adenocarcinoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
C4S dCK variant of dCK — Gemcitabine has a real, experimentally solved structure in complex with this target (PDB 2NO0, 1.8 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 geodrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2NO0 · 1.8 Å · ligand Gemcitabine (GEO). Experimental structure, not a prediction.
What the evidence adds up to
Of 684 patients with pancreatic ductal adenocarcinoma admitted to one institution between 1983 and 1989, only 118 (17%) underwent resection with curative intent. Median survival after resection was 14.3 months, compared to 4.9 months without resection. The actual 5-year survival rate was 10.2% (12 patients). Of those 12, six remained alive without evidence of disease at a median follow-up of 101 months; five died of recurrent or metastatic pancreatic cancer at 60 to 64 months, and one died of metastatic lung cancer at 84 months without evidence of recurrent pancreatic disease. The authors concluded that 5-year survival cannot be equated to cure and that pancreatectomy should be considered the best palliative procedure currently available for most patients.
A later single-institution series of 142 patients who underwent pancreatectomy for stage IA–IIB ductal adenocarcinoma between the late 1980s and 2006 reported a median survival of 21.2 months among the 137 patients who survived at least 30 days after surgery. Kaplan-Meier 3- and 5-year disease-specific survival rates were 36% and 32%, respectively. One patient survived without evidence of recurrent disease for more than 15 years. Postoperative mortality was 1.5% during the highest-volume years (2003–2006) and 3.5% for the entire cohort. The authors stated that pancreatectomy with curative intent offers a real chance of long-term survival for a disease for which there is no other curative modality.
A 2007 review noted that even with optimal surgical management, 5-year survival averages 15% to 20% for resectable disease. The authors considered the benefits of postoperative therapy for resected pancreatic ductal adenocarcinoma clear, but stated that additional benefit awaits the development of new agents, molecular targeted drugs, and novel approaches such as immunotherapy. A 2019 review described pancreatic ductal adenocarcinoma as one of the most fatal malignancies, with an extremely poor prognosis due to late diagnosis and limited response to conventional treatments, and noted that recent genomic sequencing has revealed several mutated core signalling pathways and transcriptomic subtypes.
What remains missing is a reliable method for early detection, effective systemic therapy for advanced disease, and a way to convert the majority of patients who present with unresectable disease into surgical candidates. No randomised trial has yet shown that any adjuvant regimen produces long-term survival in more than a minority of resected patients, and the molecular subtypes identified by genomic sequencing have not yet led to treatments that change the natural history of the disease for most patients.
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 the National Comprehensive Cancer Network · 2017 · 1036 citations
Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology
AbstractDuctal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection.
Annals of Surgery · 1996 · 710 citations · open access
Long-Term Survival After Curative Resection for Pancreatic Ductal Adenocarcinoma
AbstractOBJECTIVE: The authors reviewed the clinicopathologic characteristics of patients who underwent resection with curative intent for ductal adenocarcinoma of the pancreas between 1983 and 1989. SUMMARY BACKGROUND DATA: Recent studies have demonstrated a reduction in the morbidity and mortality of pancreatic resection and improvement in the actuarial 5-year survival for patients with resected ductal adenocarcinoma. METHODS: Resection with curative intent was performed on 118 of 684 patients (17%) with pancreatic cancer admitted to the authors' institution. Clinical, demographic, treatment, and pathologic variables were analyzed. The original material for all cases was reviewed; nonductal cancers were excluded. RESULTS: The head of the gland was the predominant tumor site (n = 102), followed by the body (n = 9), and tail (n = 7). Seventy-two percent of the patients underwent pancreaticoduodenectomies, 15% underwent total pancreatectomies, 10% underwent distal pancreatectomies, and 3% underwent distal subtotal pancreatectomies. Operative mortality was 3.4%. Median survival was 14.3 months after resection compared with 4.9 months if patients did not undergo resection (p < 0.0001). Twelve patients survived 5 years after surgery (10.2% overall actual 5-year survival rate). Three of the tumors were well differentiated, five were moderately differentiated, and four were poorly differentiated. Extrapancreatic invasion occurred in nine cases (75%), and perineural invasion was present in ten cases (83%). Five tumors exhibited invasion of duodenum, ampulla of Vater, and/or common bile duct, and an additional tumor invaded the portal vein. Lymph node involvement by carcinoma was noted in five cases (42%). Six patients remain alive without evidence of disease at a median follow-up of 101 months (range, 82-133 months). Five patients died of recurrent or metastatic pancreatic cancer at 60, 61, 62, 64, and 64 months, respectively. One patient died at 84 months of metastatic lung cancer without evidence of recurrent pancreatic disease. CONCLUSIONS: This paper emphasizes the grim prognosis of pancreatic ductal adenocarcinoma. Five-year survival cannot be equated to cure. Although pancreatectomy offers the only chance for long-term survival, it should be considered as the best palliative procedure currently available for the majority of patients. This emphasizes the need for the development of novel and effective adjuvant therapies for this disease.
Cancer Control · 2008 · 31 citations · open access
Outcomes following Resection of Pancreatic Adenocarcinoma: 20-Year Experience at a Single Institution
AbstractBACKGROUND: Pancreatectomy for ductal adenocarcinoma has been performed with increasing frequency since the late 1980s as postoperative mortality decreased and long-term survival became more common. However, the belief persists among some clinicians that pancreatectomy offers little survival benefit. This report reviews our institutional experience with pancreatectomy for pancreatic adenocarcinoma and provides a critical overview of the controversies regarding the benefits of surgical intervention for patients who are candidates for curative resection. METHODS: We determined the survival of 142 patients who underwent pancreatectomy for ductal adenocarcinoma with curative intent (stage IA-IIB) at Moffitt Cancer Center during the last two decades by using data obtained from review of the medical record, the Moffitt Cancer Registry, and the Social Security Death Index. Histologic diagnosis was confirmed by expert review of stained sections cut from fixed surgical specimens. RESULTS: In the 137 patients who survived at least 30 days after surgery, the median survival was 21.2 months after resection, with Kaplan-Meier 3- and 5-year disease-specific survival rates of 36% and 32%, respectively. One patient has survived without evidence of recurrent disease for more than 15 years after pancreatectomy. Survival for patients greater than 75 year of age did not differ from that of younger patients. The postoperative mortality rate was 1.5% during the most recent years of highest operative volume (2003 to 2006) and 3.5% for the entire patient cohort. CONCLUSIONS: Review of our 20-year experience with resection of pancreatic adenocarcinoma indicates that pancreatectomy with curative intent offers a real chance of long-term survival to patients with this highly lethal disease for which there is no other curative modality.
Journal of Surgical Oncology · 2007 · 23 citations
The case for routine use of adjuvant therapy in pancreatic cancer
AbstractPancreatic cancer is a devastating disease with a poor prognosis for most patients. Surgical resection remains the cornerstone of treatment, providing the only realistic hope of long-term survival. Even with optimal surgical management, 5-year survival averages 15% to 20% for resectable disease. Progress is being made, however. Currently, the benefits of postoperative therapy for resected pancreatic ductal adenocarcinoma appear clear, and recommendations for such therapy appear to us to be well justified. Additional benefit to patients awaits the development of new agents, molecular targeted drugs, and novel approaches such as immunotherapy.
International Journal of Radiation Oncology*Biology*Physics · 2022 · 12 citations · open access
Nab-Paclitaxel, Capecitabine, and Radiation Therapy After Induction Chemotherapy in Treating Patients With Locally Advanced and Borderline Resectable Pancreatic Cancer: Phase 1 Trial and Imaging-based Biomarker Validation
AbstractPURPOSE: Effective consolidative chemoradiation (CRT) regimens are lacking. In this phase 1 trial, we evaluated the safety and efficacy of nab-paclitaxel, capecitabine, and radiation therapy after induction chemotherapy in patients with locally advanced and borderline-resectable pancreatic cancer (LAPC and BRPC). Also, we evaluated a computed tomography (CT)-based biomarker of response. METHODS AND MATERIALS: ) with concurrent capecitabine and RT in cohort sizes of 3 starting at the lowest dose. Dose limiting toxicity was defined as grade 3 or higher toxicity. Patients were restaged 4 to 6 weeks post-CRT completion, and surgical resection was offered to those with stable/responsive disease. We scored the tumor interface response (IR) postchemotherapy and post-CRT into type I (remained/became more defined) and type II (became less defined). Overall survival (OS) and progression-free survival (PFS) from time of CRT were estimated using Kaplan-Meier method. P ≤ .05 was considered significant. RESULTS: Twenty-three patients started and finished on protocol (LAPC = 14, BRPC = 9). No grade 3 and 4 toxicities were reported in level 1 (n = 3) or level 2 (n = 3) initial groups. Two patients in the initial level 3 group developed dose limiting toxicity, establishing level 2 dose as the maximal tolerated dose. Level 2 group was expanded for additional 15 patients (for a total of 23 on trial), 5 of whom developed grade 3 toxicities. Seven patients underwent surgical resection. Median OS and PFS were 21.2 and 8.1 months, respectively. Type I IR was associated with better OS (P = .004) and PFS (P = .03) compared with type II IR. CONCLUSIONS: We established the maximum tolerated dose for nab-paclitaxel in a consolidative CRT regimen for pancreatic ductal adenocarcinoma. Preliminary efficacy results warrant phase 2 trial evaluation. IR may be used for personalized treatment.
Japanese Journal of Clinical Oncology · 2015 · 3 citations · open access
Feasibility of pre-operative chemoradiotherapy with gemcitabine to treat pancreatic cancer in patients with impaired renal function
AbstractOBJECTIVE: Although pre-operative chemoradiotherapy appears to be a promising treatment for patients with pancreatic ductal adenocarcinoma, there have been no reports of the feasibility of pre-operative chemoradiotherapy in pancreatic ductal adenocarcinoma patients with renal impairment. The aim of this study was to evaluate retrospectively the feasibility of pre-operative chemoradiotherapy in pancreatic ductal adenocarcinoma patients with renal impairment. METHODS: Twelve patients with resectable pancreatic ductal adenocarcinoma and a creatinine clearance of <60 ml/min were enrolled in this study. Gemcitabine-based pre-operative chemoradiotherapy was performed, followed by surgery. The feasibility of the treatment was evaluated in terms of clinical outcome and adverse events in the patients. RESULTS: All 12 patients completed gemcitabine-based pre-operative chemoradiotherapy without worsening of renal function. Restaging after the therapy revealed radiologically unresectable disease in two patients. Among the remaining 10 patients who underwent laparotomy, curative resection was performed in eight patients. After curative resection, five patients out of the eight completed post-operative adjuvant therapy. The 1- and 3-year survival rates after the start of chemoradiotherapy in the 12 patients were 80.8 and 36.9%, respectively. CONCLUSIONS: Our findings suggest that gemcitabine-based pre-operative chemoradiotherapy may be a safe and effective treatment for pancreatic ductal adenocarcinoma in patients with renal impairment.
Annals of Pancreatic Cancer · 2019 · 2 citations · open access
Genetics and biology of pancreatic cancer and its precursor lesions: lessons learned from human pathology and mouse models
AbstractAbstract: Pancreatic ductal adenocarcinoma (PDA) is one of the most fatal malignancies; it has an extremely poor prognosis due to its late diagnosis and limited response to conventional treatments. To improve PDA prognosis, new diagnostic and treatment strategies are urgently required. Recent genomic sequencing analyses revealed several mutated core signaling pathways and transcriptomic subtypes in PDA. A better understanding of PDA biology based on these genetic insights would promote the future development of novel diagnostic methods and treatments. In this review, we summarize our current understanding of PDA genetics and biology, predominantly via insights from mouse model studies.
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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