DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for small intestine neuroendocrine tumor — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSmall intestine neuroendocrine tumor maps to a 4-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 small intestine 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
leukotriene A4 hydrolase (LTA4H) — LTA4H 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 2rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3FUN · 1.58 Å · ligand {4-[(2R)-pyrrolidin-2-ylmethoxy]phenyl}(4-thiophen-3-ylphenyl)methanone (798). Experimental structure, not a prediction.
What the evidence adds up to
Small intestinal neuroendocrine tumours are the most common primary malignancy of the small bowel, and their incidence has been increasing worldwide over recent decades. The indolent nature of these tumours often leads to a delayed diagnosis, with more than one-third of patients presenting with synchronous metastases at the time of detection. Primary tumour resection remains the only curative option. The 2017 ENETS consensus guidelines note that the low incidence and wide heterogeneity in biological behaviour make it difficult to standardise surgical indications, and the guidelines represent a consensus of the working group rather than a definitive protocol.
A 2013 review of molecular pathogenesis reports that small intestinal neuroendocrine tumours are genetically characterised by an absence of alterations to K-ras, p53 and DNA mismatch repair genes. Loss of chromosome 18, deletion of Smad2 and Smad4, and amplification of SRC, EGFR and PDGFR have been reported. Abnormal DNA methylation status, including overexpression of DNA methyltransferase, higher methylation of the RASSF1A promoter, and overexpression of histone H1x, are also associated with these tumours. The tumours are associated with fibrosis, possibly due to high levels of serotonin and other fibrotic factors. Genetic studies have identified genes that can differentiate small intestinal neuroendocrine tumours from other neuroendocrine tumours (oxytocin receptor, G protein-coupled receptor 113, VMAT-1, CDX-2), enabling more accurate diagnosis. Paraneoplastic antigen Ma2, neurokinin A and the CART peptide are under investigation as prognostic biomarkers, but the review states there is still an unmet need for more sensitive biomarkers for earlier diagnosis and for a more specific classification system that encompasses tumour histology and reliable predictors of clinical response.
A 2014 review of hormonal treatment updates for gastroenteropancreatic neuroendocrine tumours notes that these tumours remain difficult to treat with conventional cytotoxic regimens. The review highlights two specific abstracts (#268 and #273) from the 2014 ASCO Gastrointestinal Cancers Symposium that shed light on a novel, targeted means of treatment, but no concrete survival or response rate data from those abstracts are provided in the review itself.
What is still missing is a reliable set of biomarkers that can enable earlier diagnosis and predict clinical response, a standardised surgical approach that accounts for tumour heterogeneity, and prospective trial data that demonstrate whether the molecular targets identified (SRC, EGFR, PDGFR, DNA methylation pathways) can be translated into effective therapies with measurable survival or response-rate improvements.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neuroendocrinology · 2017 · 297 citations · open access
ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumours: Surgery for Small Intestinal and Pancreatic Neuroendocrine Tumours
AbstractThe small intestine and pancreas are among the most frequent abdominal sites of origin of neuroendocrine tumours. Distinctive features of these forms are represented by the relatively low incidence and the wide heterogeneity in biological behaviour. In this light, it is difficult to standardize indications for surgery and the most appropriate approach. It would be helpful for surgeons managing patients with these tumours to have guidelines for surgical treatment of small intestinal neuroendocrine tumours and pancreatic neuroendocrine tumours. The proposed guidelines represent a consensus of the working group of the European Neuroendocrine Tumor Society (ENETS).
Endokrynologia Polska · 2022 · 46 citations · open access
Update of the diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours) [Aktualizacja zaleceń ogólnych dotyczących postępowania diagnostyczno-terapeutycznego w nowotworach neuroendokrynnych układu pokarmowego (rekomendowane przez Polską Sieć Guzów Neuroendokrynnych)]
AbstractContinuous progress in the diagnostics and treatment of neuroendocrine neoplasms (NENs), the emerging results of new clinical trials, and the new guidelines issued by medical societies have prompted experts from the Polish Network of Neuroendocrine Tumours to update the 2017 recommendations regarding the management of neuroendocrine neoplasms. This article presents the general recommendations for the management of NENs, resulting from the findings of the experts participating in the Fourth Round Table Conference, entitled "Polish Guidelines for the Diagnostics and Treatment of Neuroendocrine Neoplasms of the gastrointestinal tract, Żelechów, June 2021". Drawing from the extensive experience of centres treating these cancers, we hope that we have managed to formulate the optimal method of treating patients with NENs, applying the latest reports and achievements in the field of medicine, which can be effectively implemented in our country. The respective parts of this work present the approach to the management of: NENs of the stomach and duodenum (including gastrinoma), pancreas, small intestine, and appendix, as well as large intestine.
World Journal of Gastrointestinal Surgery · 2023 · 9 citations · open access
Surgical aspects of small intestinal neuroendocrine tumors
AbstractSmall intestinal neuroendocrine tumors (NETs) are a heterogeneous group of epithelial tumors with a predominant neuroendocrine differentiation. Although NETs are usually considered rare neoplasms, small intestinal NETs are the most common primary malignancy of the small bowel, with an increasing prevalence worldwide during the course of the past few decades. The indolent nature of these tumors often leads to a delayed diagnosis, resulting in over one-third of patients presenting with synchronous metastases. Primary tumor resection remains the only curative option for this type of tumor. In this review article, the various surgical aspects for the excision of small intestinal NETs are discussed.
AbstractGastroenteropancreatic neuroendocrine tumors are a heterogeneous group of carcinomas that remain difficult to treat with conventional cytotoxic regimens. The 2014 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium brought us new insights into the management of gastroenteropancreatic neuroendocrine tumors. The focus of this review will serve to highlight specific Abstracts (#268 and #273) that help shed light on a novel, targeted means of treating gastroenteropancreatic neuroendocrine tumors.
Gastrointestinal Tumors · 2013 · 3 citations · open access
Current Perspective on the Pathogenesis of Small Intestinal Neuroendocrine Tumors: Progress in Biomarkers and Molecular Events
Abstract<b><i>Background:</i></b> Neuroendocrine tumors of the gastrointestinal tract differ in their histopathologic and clinical presentation. Small intestinal neuroendocrine tumors (SI-NETs), representing only a small portion within gastrointestinal malignancies, are often associated with a delayed diagnosis due to their non-specific symptoms. The increased incidence of SI-NETs during the last decades demands earlier diagnosis and more effective treatment, which both rely on a better understanding on the underlying molecular mechanisms. <b><i>Summary:</i></b> The purpose of this review is to discuss the biomolecular changes responsible for the pathogenesis of SI-NETs, and potential biomarkers in the diagnostic and prognostic evaluation. <b>Key Message</b> A greater understanding of the molecular mechanisms that underpin the pathogenesis of small intestinal neuroendocrine tumors (SI-NETs) facilitates the classification, diagnosis and treatment of these relatively rare gastrointestinal malignancies. <b>Practical Implications</b> Currently, SI-NETs are diagnosed using histological examination and staining for various neuroendocrine markers. Genetically, SI-NETs are characterized by an absence of alterations to K-ras, p53 and DNA mismatch repair genes. Loss of chromosome 18, deletion of Smad2 and Smad4, and amplification of SRC, EGFR and PDGFR have been reported. Abnormal DNA methylation status, reflected by overexpression of DNA methyltransferase, higher methylation of the RASSF1A promoter and overexpression of histone H1x are also associated with SI-NETs. These tumors are also associated with fibrosis, possibly due to the high levels of serotonin and other fibrotic factors produced. Genetic studies have pinpointed genes that can differentiate SI-NETs from other neuroendocrine tumors (oxytocin receptor, G protein-coupled receptor 113, VMAT-1, CDX-2), enabling more accurate diagnosis. Paraneoplastic antigen Ma2, neurokinin A and the CART peptide are under investigation as prognostic biomarkers. There is, however, still an unmet need for more sensitive biomarkers for earlier diagnosis and for a more specific classification system that encompasses tumor histology and reliable predictors of clinical response.
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.
