ArticleJCI insight2018
Repurposing sertraline sensitizes non-small cell lung cancer cells to erlotinib by inducing autophagy.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Antidepressant Use and Lung Cancer Risk and Survival: A Meta-analysis of Observational Studies.Cancer research communications · 2023Pooled it
- Integrated computational and preclinical evaluation of drug repurposing candidates for KRAS-mutant non-small cell lung cancer.Scientific reports · 2026Article
- An Overview of the Potential Use of Selective Serotonin Reuptake Inhibitors (SSRIs) in Cancer Treatment.Current cancer drug targets · 2026Review
- The dual role of sertraline: From antidepressant to antifungal drug with broad metabolic disruption.Genetics and molecular biology · 2026Article
- Repurposing the Antidepressant Sertraline: A Systematic Scoping Review of Its Anticancer Mechanisms.Pharmacology research & perspectives · 2025Article
- Review
- Machine Learning Model for Predicting Sertraline-like Activities and Its Impact on Cancer Chemosensitization.ACS chemical neuroscience · 2025Article
- An overview of autophagy inhibition as a potential clinical strategy in cancer therapy.Molecular pharmacology · 2025Review
- The Use of Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants in the Treatment of Lung Cancer.International journal of molecular sciences · 2025Review
- Cytotoxic Effect of Escitalopram/Etoposide Combination on Etoposide-Resistant Lung Cancer.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Repurposing of nervous system drugs for cancer treatment: recent advances, challenges, and future perspectives.Discover oncology · 2025Review
- Comparison and Analysis of the Drug-Resistance Mechanism of Osimertinib- and Almonertinib-Resistant Cell Lines.Analytical cellular pathology (Amsterdam) · 2025Article
- Sertraline/chloroquine combination therapy to target hypoxic and immunosuppressive serine/glycine synthesis-dependent glioblastomas.Oncogenesis · 2024Article
- Is Autophagy Targeting a Valid Adjuvant Strategy in Conjunction with Tyrosine Kinase Inhibitors?Cancers · 2024Review
- Antidepressant Sertraline Synergistically Enhances Paclitaxel Efficacy by Inducing Autophagy in Colorectal Cancer Cells.Molecules (Basel, Switzerland) · 2024Article
- Erlotinib Treatment in Colorectal Cancer Suppresses Autophagy Based onCurrent issues in molecular biology · 2024Article
- Serotonin signalling in cancer: Emerging mechanisms and therapeutic opportunities.Clinical and translational medicine · 2024Review
- Modulation of ACE2/Ang1-7/Mas and ACE/AngII/AT1 axes affects anticancer properties of sertraline in MCF-7 breast cancer cells.Biochemistry and biophysics reports · 2024Article
- Beyond Psychotropic: Potential Repurposing of Fluoxetine toward Cancer Therapy.International journal of molecular sciences · 2024Review
- A Surprising Repurposing of Central Nervous System Drugs against Squamous Cell Carcinoma of the Bladder, UM-UC-5.Pharmaceutics · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Lung cancer patients treated with tyrosine kinase inhibitors (TKIs) often develop resistance. More effective and safe therapeutic agents are urgently needed to overcome TKI resistance. Here, we propose a medical genetics-based approach to identify indications for over 1,000 US Food and Drug Administration-approved (FDA-approved) drugs with high accuracy. We identified a potentially novel indication for an approved antidepressant drug, sertraline, for the treatment of non-small cell lung cancer (NSCLC). We found that sertraline inhibits the viability of NSCLC cells and shows a synergy with erlotinib. Specifically, the cotreatment of sertraline and erlotinib effectively promotes autophagic flux in cells, as indicated by LC3-II accumulation and autolysosome formation. Mechanistic studies further reveal that dual treatment of sertraline and erlotinib reciprocally regulates the AMPK/mTOR pathway in NSCLC cells. The blockade of AMPK activation decreases the anticancer efficacy of either sertraline alone or the combination. Efficacy of this combination regimen is decreased by pharmacological inhibition of autophagy or genetic knockdown of ATG5 or Beclin 1. Importantly, our results suggest that sertraline and erlotinib combination suppress tumor growth and prolong mouse survival in an orthotopic NSCLC mouse model (P = 0.0005). In summary, our medical genetics-based approach facilitates discovery of new anticancer indications for FDA-approved drugs for the treatment of NSCLC.
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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.