DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for pulmonary neuroendocrine tumor — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePulmonary neuroendocrine tumor maps to a 2-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
approvedEverolimusApproved drug
Structures already discussed alongside pulmonary neuroendocrine tumor in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Cytochrome P450 107G1 (RapN) — Everolimus has a real, experimentally solved structure in complex with this target (PDB 6L3A, 3.0 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 e53drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6L3A · 3.0 Å · ligand Everolimus (E53). Experimental structure, not a prediction.
What the evidence adds up to
Pulmonary neuroendocrine tumours account for about 25% of all neuroendocrine neoplasms, but typical and atypical carcinoids of the lung are rare, making up only 1–2% of all lung cancers. Distant metastases occur in 2–14% of cases. For local disease, surgery is the mainstay of treatment. In advanced disease, no antiproliferative drugs are approved specifically for lung carcinoids, and none of the currently available agents provide a cure. Treatment options include somatostatin analogues, mTOR inhibitors, angiogenesis inhibitors, systemic chemotherapy, and radiolabelled somatostatin analogues, but the evidence comes almost entirely from small, retrospective phase II studies. Randomised phase II and III trials were reported as underway in 2014.
A 1988 study described the first reproducible induction of pulmonary neuroendocrine cancer in a hamster model, showing that deviations from normal pulmonary oxygen levels may be essential for tumour induction. That model was intended to facilitate studies of pathophysiology, biochemistry, and therapy, but no therapeutic results from it are reported in the provided abstracts.
In 2022, the first patient-derived tumour organoids (PDTOs) from pulmonary neuroendocrine tumours and from large cell neuroendocrine carcinoma were established. These organoids maintained the gene expression patterns, intra-tumoural heterogeneity, and evolutionary processes of the original tumours. Drug sensitivity testing in the organoids uncovered therapeutic sensitivities to an inhibitor of NAD salvage biosynthesis and to an inhibitor of BCL-2. The pulmonary neuroendocrine tumour organoids showed a dependency on EGF, and analysis of an independent cohort found that approximately 50% of pulmonary neuroendocrine tumours expressed EGFR. The study identifies a potentially actionable vulnerability for a subset of these neoplasms, but it is an in vitro finding.
What is still missing are large, randomised clinical trials that test these candidate vulnerabilities in patients, adequate funding for such trials given the rarity of the disease, and validated patient stratification methods to identify which subset of tumours might respond to NAD salvage or BCL-2 inhibition. The existing clinical evidence remains limited to small retrospective studies, and no drug has been shown to cure advanced pulmonary neuroendocrine tumours.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Carcinogenesis · 1988 · 74 citations
An animal model for neuroendocrine lung cancer
AbstractNeuroendocrine lung cancer is among the most common types of lung tumor in man and demonstrates a strong etiological association with cigarette smoking. However, despite numerous efforts, this cancer type has never been induced in animals. This report describes, for the first time, the reproducible induction of pulmonary neuroendocrine cancer in a readily available hamster model. The data provide evidence that deviations from pre-existing normal pulmonary oxygen levels may be an essential factor for the induction of this malignancy. This new model should greatly facilitate studies of the pathophysiology, biochemistry and therapy of neuroendocrine cancer of the lung.
Annals of Translational Medicine · 2018 · 29 citations · open access
Advances on systemic treatment for lung neuroendocrine neoplasms
AbstractLung well-to-moderately differentiated neuroendocrine tumors (also known as carcinoids) and large cell neuroendocrine lung carcinoma (poorly differentiated neuroendocrine tumor) are rare neuroendocrine neoplasms, which account for less than 4% of all lung neoplasms. Due to their low incidence, their systemic treatment is greatly influenced by therapeutic evidence derived from the more frequent gastroenteropancreatic neuroendocrine neoplasms and/or small cell lung carcinoma leading to significant bias. Currently, employed systemic therapies for lung carcinoids, aiming at controlling tumor growth include long acting somatostatin analogues (SSAs), peptide receptor radionuclide therapy, chemotherapy and molecular-targeted therapy. In this review, each of those treatments is presented based upon available clinical evidence from retrospective and prospective studies particularly focused on the role of everolimus in the advanced setting and on ongoing clinical trials reflecting our expectations in the near future. In addition, we critically analyse currently employed treatment of large cell neuroendocrine carcinoma where the appropriate chemotherapeutic regimen is still a matter of debate.
Case Reports in Oncology · 2013 · 5 citations · open access
Long-Term Management of a Patient with Well-Differentiated Pulmonary Neuroendocrine Carcinoma: A Case Report
AbstractPulmonary neuroendocrine tumors (NET) are rare, and very few published reports have described the long-term treatment of patients with this disease. Current treatment options for patients with metastatic well-differentiated pulmonary NET are limited. This case report details the long-term treatment of a 62-year-old female patient with well-differentiated pulmonary NET and multiple liver metastases. The heavily pretreated patient achieved radiographic stability in measurable disease, improvement in nonmeasurable disease, and symptomatic improvement over 3 years while receiving the combination of everolimus and octreotide long-acting repeatable (LAR). Treatment was well tolerated without mucositis, rash, or pneumonitis. This case report suggests that the combination of everolimus and octreotide LAR may be a novel treatment option for heavily pretreated patients with metastatic well-differentiated pulmonary NET, but these findings require further analysis in clinical trials.
International Journal of Endocrine Oncology · 2014 · 1 citations
Neuroendocrine Tumors of the Lung: A Comprehensive Overview
AbstractA total of 25% of neuroendocrine tumors originate in the lung. Still, typical and atypical carcinoids of the lung are rare, accounting for only 1–2% of all lung cancers. Distant metastases are infrequent, occurring in 2–14% of cases. The mainstay of treatment of local disease is surgery. In advanced disease there are no antiproliferative agents approved for carcinoids of the lung. None of the currently available drugs provide a cure. There are several treatment options, such as somatostatin analogs, mTOR inhibition, inhibitors of angiogenesis, systemic chemotherapy and radiolabeled somatostatin analogs. Interpretation of the data is complicated, since it mainly consists of small (retrospective) Phase II studies. Fortunately, randomized Phase II and III studies are underway. This article emphasizes the specific features of neuroendocrine tumors in the lung and focuses on the treatment in advanced disease.
bioRxiv (Cold Spring Harbor Laboratory) · 2022 · 1 citations · open access
Druggable Growth Dependencies and Tumor Evolution Analysis in Patient-Derived Organoids of Neuroendocrine Cancer
AbstractSUMMARY Neuroendocrine neoplasms (NENs) comprise well-differentiated neuroendocrine tumors and poorly-differentiated carcinomas. Treatment options for patients with NENs are limited, in part due to lack of accurate models. To address this need we established the first patient-derived tumor organoids (PDTOs) from pulmonary neuroendocrine tumors and derived PDTOs from an understudied NEN subtype, large cell neuroendocrine carcinoma (LCNEC). PDTOs maintain the gene expression patterns, intra-tumoral heterogeneity, and evolutionary processes of parental tumors. Through drug sensitivity analyses, we uncover therapeutic sensitivities to an inhibitor of NAD salvage biosynthesis and to an inhibitor of BCL-2. Finally, we identify a dependency on EGF in pulmonary neuroendocrine tumor PDTOs. Consistent with these findings, analysis of an independent cohort showed that approximately 50% of pulmonary neuroendocrine tumors expressed EGFR. This study identifies a potentially actionable vulnerability for a subset of NENs, and further highlights the utility of these novel PDTO models for the study of NENs. Graphical abstract Highlights PDTOs of pulmonary NETs and LCNEC were established PDTOs recapitulate intra-tumoral heterogeneity and evolution of parental tumors Drug assays reveal therapeutic vulnerabilities and biomarkers Pulmonary NET PDTOs are dependent on EGF
Progress on diagnosis and treatment of lung neuroendocrine tumors
AbstractNeuroendocrine tumors (NETs) are the malignant tumors which originate from neuroendocrine cells of the whole body, the lung is the second common site after the gastrointestinal tract.The lung NETs have four subtypes: typical carcinoids, atypical carcinoids, large cell neuroendocrine carcinoma and small cell lung carcinoma.Compared with the common lung cancers, lung NETs have different pathology, clinical manifestations and treatment.This article reviews the progress of the diagnosis and treatment of pulmonary NETs in recent years.
Key words:
Lung neuroendocrine tumors; Diagnosis; Treatment
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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