DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for pancreatic neuroendocrine tumor — 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 neuroendocrine tumor 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
No approved-drug candidate for pancreatic neuroendocrine tumor 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
endothelial PAS domain protein 1 (EPAS1) — EPAS1 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 furan-2-ylmethyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3H82 · 1.5 Å · ligand N-(furan-2-ylmethyl)-2-nitro-4-(trifluoromethyl)aniline (020). Experimental structure, not a prediction.
What the evidence adds up to
The North American Neuroendocrine Tumor Society consensus paper from 2019 on surgical management of pancreatic neuroendocrine tumours does not report any new clinical trial data, survival figures, or response rates; it summarises expert opinion on surgical questions based on literature available up to July 2018. A 2015 review of genetics notes that recent sequencing studies have identified cellular processes altered in pancreatic neuroendocrine tumours and pointed to pathways for targeted therapies, but it provides no patient outcomes or numbers. A 2016 meta-analysis of randomised phase III trials included 1,908 cases (1,012 in the experimental arm, 896 in the control arm). Pooled analysis showed that targeted agents significantly increased progression-free survival compared to control (hazard ratio 0.59, 95% CI 0.42–0.84, P = 0.003), with a subgroup analysis favouring pancreatic neuroendocrine tumours. Overall survival improved (hazard ratio 0.79, 95% CI 0.63–0.98, P = 0.03) and response rate increased (hazard ratio 3.33, 95% CI 2.02–5.49, P < 0.00001) across all neuroendocrine tumour types. The authors conclude the analysis supports routine use of targeted agents, particularly for pancreatic neuroendocrine tumours.
A 2012 review states that poorly differentiated pancreatic neuroendocrine tumours can behave aggressively, with 5-year survival ranging from 31% to 48%, and that recent data show a doubling of progression-free survival with treatments targeting molecular changes in unresectable disease. A 2016 review of molecular pathology notes that the incidence of pancreatic neuroendocrine tumours is growing rapidly but that research lags behind other pancreatic tumours, and that several potential targets have shown application in treatment. A 2020 book on pancreatic cancer states that pancreatic cancer remains one of the most lethal solid organ tumours with a poor five-year survival rate despite current advances, and covers diagnostic tools, treatment strategies, and mechanisms of therapy resistance for both pancreatic cancer and pancreatic neuroendocrine tumours.
What is still missing are large, prospective, randomised trials that stratify patients by tumour grade, genetic subtype, and prior treatments; consistent funding for such trials given the relative rarity of the disease; and validated biomarkers to predict which patients will benefit from which targeted agent. The meta-analysis pooled heterogeneous studies, and the survival gains, while statistically significant, are modest in absolute terms. No abstract provides data on long-term toxicity or quality of life with these agents.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Pancreas · 2019 · 389 citations · open access
The North American Neuroendocrine Tumor Society Consensus Paper on the Surgical Management of Pancreatic Neuroendocrine Tumors
AbstractThis manuscript is the result of the North American Neuroendocrine Tumor Society consensus conference on the surgical management of pancreatic neuroendocrine tumors from July 19 to 20, 2018. The group reviewed a series of questions of specific interest to surgeons taking care of patients with pancreatic neuroendocrine tumors, and for each, the available literature was reviewed. What follows are these reviews for each question followed by recommendations of the panel.
Genetics of pancreatic neuroendocrine tumors: implications for the clinic
AbstractPancreatic neuroendocrine tumors (PanNETs) are a common and deadly neoplasm of the pancreas. Although the importance of genetic alterations in PanNETs has been known for many years, recent comprehensive sequencing studies have greatly expanded our knowledge of neuroendocrine tumorigenesis in the pancreas. These studies have identified specific cellular processes that are altered in PanNETs, highlighted alterations with prognostic implications, and pointed to pathways for targeted therapies. In this review, we will discuss the genetic alterations that play a key role in PanNET tumorigenesis, with a specific focus on those alterations with the potential to change the way patients with these neoplasms are diagnosed and treated.
Cancer Biology & Therapy · 2016 · 9 citations · open access
Role of targeted agents in neuroendocrine tumors: Results from a meta-analysis
AbstractBACKGROUND: Several randomized phase III trials in neuroendocrine tumors (NETs) showed the clinical role of new targeted agents and their impact on tumor response and outcome of whose patients affected by advanced NET. In this study, we summarize the available clinical data related to clinical efficacy of targeted therapies in the treatment of advanced NETs. METHODS: A meta-analysis of randomized studies in accordance with the PRISMA guidelines was performed after searching the databases of PubMed, the Cochrane Library, and the ASCO University Meeting for relevant publications. RESULTS: One thousand 9 hundred and 8 cases were included in the meta-analysis; among these, 1012 were in the experimental arm and 896 were in the control arm. The pooled analysis of the use of target agents in NETs revealed significantly increased of progression free survival compared to control group (hazard ratio = 0.59, 95% CI:0.42-0.84; P = 0.003). Subgroup analysis of patients according to tumor site showed a difference in favor of pancreatic neuroendocrine tumors. Moreover, targeted therapies improved the overall survival (hazard ratio = 0.79, 95%CI: 0.63-0.98; P = 0.03), and response rate (hazard ratio = 3.33, 95% CI 2.02-5.49; P < 0.00001) in all types of NETs. CONCLUSION: Our analysis supports the routine use of targeted agents for treatment of neuroendocrine tumors with particular regards to the pancreatic neuroendocrine tumors.
Advances in the treatment of pancreatic neuroendocrine tumours
AbstractPancreatic neuroendocrine tumours (pNETs) are relatively rare and generally felt to follow an indolent course. But poorly differentiated tumours can behave aggressively with 5-year survival ranging from 31% to 48%. Recent data suggest that patients with pNETs may derive benefit from treatment targeting the molecular changes expressed in this tumour group. This article describes advances in the treatment of unresectable pNETs that have led to a doubling of progression free survival.
Progression on molecular pathology of pancreatic neuroendocrine tumors
AbstractPancreatic neuroendocrine tumors (PNET) is a complicated and heterogeneous group of neoplasia, and the incidence of PNET is growing rapidly recently. The current study on PNET lags behind what is known of other pancreatic tumors. Therefore, understanding of the molecular pathology is important for improving the early diagnosis, treatment and prognosis. With the development of molecular biology, there are already several potential targets proved to have application role in treatment of PNET. Here, the authors present the current knowledge about the molecular alterations of PNET.
Key words:
Pancreatic neuroendocrine tumors; Molecular pathology; Signal transduction
IntechOpen eBooks · 2020 · 0 citations · open access
Challenges in Pancreatic Cancer
AbstractPancreatic cancer is one of the most lethal solid organ tumors with a poor five-year survival rate despite current oncological advances. The early and proper diagnosis of pancreatic cancer is of great importance for the improvement of the overall prognosis. This book provides an overview of the current challenges and states of pancreatic cancer and pancreatic neuroendocrine tumors, including information on diagnostic tools, treatment strategies, and mechanisms of pancreatic cancer therapy resistance.
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.
