ArticleCancer discovery2013
A drug repositioning approach identifies tricyclic antidepressants as inhibitors of small cell lung cancer and other neuroendocrine tumors.
Article in Cancer discovery, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 211 papers, 4 of them syntheses that pooled it.
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Who cites it
211 citing papers in PubMed, 4 syntheses or guidelines pooled it, 363 citations in OpenAlex.
- Association between antidepressant use and gynecological cancer risk: a systematic review and meta-analysis.European journal of clinical pharmacology · 2025Pooled it
- Critical period plasticity-related transcriptional aberrations in schizophrenia and bipolar disorder.Schizophrenia research · 2019Pooled it
- Meta- and cross-species analyses of insulin resistance based on gene expression datasets in human white adipose tissues.Scientific reports · 2018Pooled it
- Prioritizing therapeutics for lung cancer: an integrative meta-analysis of cancer gene signatures and chemogenomic data.PLoS computational biology · 2015Pooled it
- Repurposing Antipsychotics in Cancer Therapy: Modulation of Autophagy Mechanisms.Clinical drug investigation · 2026Review
- Alprazolam Reduces Inflammatory Cytokine Production in Pancreatic Cancer-Associated Fibroblasts.Cancer research communications · 2026Article
- Cell line-specific antileukemic effects of imipramine: apoptosis, reactive oxygen species modulation and cytokine responses in human acute promyelocytic leukemia and chronic myelogenous leukemia cells.Molecular biology reports · 2026Article
- An integrated drug repositioning analysis identifies rosiglitazone as a treatment for sarcopenia.Communications biology · 2026Article
- c-JUN enhances CRISPR knockin anti-B7-H3 CAR T cell function in small cell lung cancer and thoracic SMARCA4-deficient undifferentiated tumors.Cell reports. Medicine · 2026Article
- Phenothiazine Derivatives and Their Impact on the Apoptosis Processes: A Review.Journal of applied toxicology : JAT · 2026Review
- Next Generation Calcium Nanomaterials: Disrupting Tumor CaInternational journal of nanomedicine · 2026Review
- CyTOF-based profiling of circulating tumor cells predicts aggressiveness and therapy response in SCLC liquid biopsies at a personalized level.bioRxiv : the preprint server for biology · 2025Article
- Drug Repositioning for HPV Clade-Specific Cervicouterine Cancer Using the OCTAD Pipeline.International journal of molecular sciences · 2025Article
- Drug repurposing in cancer research: a bibliometric analysis.Discover oncology · 2025Article
- Article
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- Exploring potential biomarkers and lead molecules in gastric cancer by network biology, drug repurposing and virtual screening strategies.Molecular diversity · 2025Article
- Cancer-nervous system crosstalk: from biological mechanism to therapeutic opportunities.Molecular cancer · 2025Review
- Repurposing of nervous system drugs for cancer treatment: recent advances, challenges, and future perspectives.Discover oncology · 2025Review
- Neuronal mimicry in tumors: lessons from neuroscience to tackle cancer.Cancer metastasis reviews · 2025Review
151 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledSmall cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with high mortality. We used a systematic drug repositioning bioinformatics approach querying a large compendium of gene expression profiles to identify candidate U.S. Food and Drug Administration (FDA)-approved drugs to treat SCLC. We found that tricyclic antidepressants and related molecules potently induce apoptosis in both chemonaïve and chemoresistant SCLC cells in culture, in mouse and human SCLC tumors transplanted into immunocompromised mice, and in endogenous tumors from a mouse model for human SCLC. The candidate drugs activate stress pathways and induce cell death in SCLC cells, at least in part by disrupting autocrine survival signals involving neurotransmitters and their G protein-coupled receptors. The candidate drugs inhibit the growth of other neuroendocrine tumors, including pancreatic neuroendocrine tumors and Merkel cell carcinoma. These experiments identify novel targeted strategies that can be rapidly evaluated in patients with neuroendocrine tumors through the repurposing of approved drugs. SIGNIFICANCE: Our work shows the power of bioinformatics-based drug approaches to rapidly repurpose FDA-approved drugs and identifies a novel class of molecules to treat patients with SCLC, a cancer for which no effective novel systemic treatments have been identified in several decades. In addition, our experiments highlight the importance of novel autocrine mechanisms in promoting the growth of neuroendocrine tumor cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.