ArticleNature cancer2020
EGFR inhibition triggers an adaptive response by co-opting antiviral signaling pathways in lung cancer.
Article in Nature cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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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
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Pooled it
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- Tumor microenvironment and signaling pathways in melanoma brain metastasis.Annals of translational medicine · 2026Review
- Concurrent genetic and non-genetic resistance mechanisms to KRAS inhibition in colorectal cancer.Cancer cell · 2026Article
- Developmental programmes drive cellular plasticity, disease progression and therapy resistance in lung adenocarcinoma.Molecular oncology · 2026Article
- Stimulator of interferon genes agonist augmented antitumor immunity of osimertinib in Egfr-mutated lung cancer.Molecular oncology · 2026Article
- WNT inhibition activates interferon stimulated gene expression by alleviating epigenetic repression of endogenous retroviruses.Scientific reports · 2026Article
- KRAS mutated lung adenocarcinoma responds to pan-ERBB and Aurora kinase inhibitors.NPJ precision oncology · 2026Article
- IFITM3-MET interaction drives osimertinib resistance through AKT pathway activation in EGFR-mutant non-small cell lung cancer.Molecular cancer · 2025Article
- Interferon Epsilon Loss Is Elusive 9p21 Link to Immune-Cold Tumors, Resistant to Immune Checkpoint Therapy, and Endogenous CXCL9/10 Induction.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025Review
- EGFR: New Insights on Its Activation and Mutation in Tumor and Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- VDR Decrease Enhances the Efficacy of 1,25-Dihydroxyvitamin D3 Inhibiting Gefitinib Resistance by Regulating EGFR/FASN Loop in NSCLC Cells.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Targeting Metabolic Vulnerabilities Reveals Hexokinase 2 as a Key Mediator of Resistance to Osimertinib in Non-Small Cell Lung Cancer Models.ACS pharmacology & translational science · 2025Article
- Anti-galectin-9 therapy synergizes with EGFR inhibition to reprogram the tumor microenvironment and overcome immune evasion.Journal for immunotherapy of cancer · 2025Article
- Integrative transcriptomic analysis identifies emetine as a promising candidate for overcoming acquired resistance to ALK inhibitors in lung cancer.Molecular oncology · 2025Article
- Anti-EGFR aptamer exhibits direct anti-cancer effects in NSCLC cells harboring EGFR L858R mutations.NPJ precision oncology · 2024Article
- Inflammatory signaling in targeted therapy resistance: focus on EGFR-targeted treatment.Cancer biology & medicine · 2024Article
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
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20 authors at 4 institutions in 1 country.
Funding
Abstract
EGFR inhibition is an effective treatment in the minority of non-small cell lung cancer (NSCLC) cases harboring EGFR-activating mutations, but not in EGFR wild type (EGFRwt) tumors. Here, we demonstrate that EGFR inhibition triggers an antiviral defense pathway in NSCLC. Inhibiting mutant EGFR triggers Type I IFN-I upregulation via a RIG-I-TBK1-IRF3 pathway. The ubiquitin ligase TRIM32 associates with TBK1 upon EGFR inhibition, and is required for K63-linked ubiquitination and TBK1 activation. Inhibiting EGFRwt upregulates interferons via an NF-κB-dependent pathway. Inhibition of IFN signaling enhances EGFR-TKI sensitivity in EGFR mutant NSCLC and renders EGFRwt/KRAS mutant NSCLC sensitive to EGFR inhibition in xenograft and immunocompetent mouse models. Furthermore, NSCLC tumors with decreased IFN-I expression are more responsive to EGFR TKI treatment. We propose that IFN-I signaling is a major determinant of EGFR-TKI sensitivity in NSCLC and that a combination of EGFR TKI plus IFN-neutralizing antibody could be useful in most NSCLC patients.
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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.