ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
The Allelic Context of the C797S Mutation Acquired upon Treatment with Third-Generation EGFR Inhibitors Impacts Sensitivity to Subsequent Treatment Strategies.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 316 papers, 1 of them a synthesis that pooled it.
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Who cites it
316 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Patterns and Treatment Strategies of Osimertinib Resistance in T790M-Positive Non-Small Cell Lung Cancer: A Pooled Analysis.Frontiers in oncology · 2021Pooled it
- Osimertinib plus Gefitinib in Patients with EGFR-Mutated Advanced Non-Small Cell Lung Cancer and EGFR (C797X) Mutation Following First-Line Osimertinib: ORCHARD.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- A Phase II trial of alternating osimertinib and gefitinib therapy in advanced EGFR-T790M positive non-small cell lung cancer: OSCILLATE.Nature communications · 2024Trial
- Identification of optimal dosing schedules of dacomitinib and osimertinib for a phase I/II trial in advanced EGFR-mutant non-small cell lung cancer.Nature communications · 2021Trial
- Prospective detection of mutations in cerebrospinal fluid, pleural effusion, and ascites of advanced cancer patients to guide treatment decisions.Molecular oncology · 2019Trial
- In Pursuit of Enduring Inactivation: A Perspective on the Development and Study of Irreversible-Covalent Inhibitors.Biochemistry · 2026Review
- Oncogenic mutations in non-small cell lung cancer: from molecular mechanisms to clinical practice.Signal transduction and targeted therapy · 2026Review
- Efficacy and safety of third-generationTranslational lung cancer research · 2026Article
- Hydrophobic Tag Protein Degraders: An Emerging Therapeutic Strategy for Cancer.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Multiparatopic antibodies overcome tyrosine kinase inhibitor resistance by inducing lysosomal degradation of EGFR mutants.Oncogene · 2026Article
- Inhibition of PGC1β-dependent mitochondrial biogenesis enhances EGFR-targeted therapy in lung cancer.EMBO molecular medicine · 2026Article
- Clinical utility of comprehensive genomic profiling in thoracic malignancies beyond conventional gene testing.International journal of clinical oncology · 2026Article
- Mycoplasma infection drives EGFR-TKI resistance through convergent transcriptomic reprogramming in non-small cell lung cancer.iScience · 2026Article
- Epidermal Growth Factor Receptor as a Model Drug Target for Scrutinizing the Status Quo in Drug Discovery and Chemical Biology.ACS bio & med chem Au · 2026Review
- A Non-Canonical Core Transcriptional Regulatory Circuit Orchestrates Chromatin Reprogramming to Drive Osimertinib Resistance in Non-Small Cell Lung Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Exploiting the T790M Gatekeeper: A Theoretical Blueprint for Non-Covalent Inhibition of inPharmaceutics · 2026Article
- Opportunities and challenges in the development of evolving EGFR inhibitors to overcome EGFR TKIs resistance.Acta pharmacologica Sinica · 2026Review
- Treatment-Emergent Isolated EGFR C797S Mutation Following First-Line Osimertinib-Based Combination Therapy: A Case Report and Literature Review.Respirology case reports · 2026Article
- Integrative structural and dynamics studies of epidermal growth factor receptor (EGFR).Experimental & molecular medicine · 2026Review
- JIN-A02, a Mutant-Selective Fourth-Generation EGFR Inhibitor, Overcomes C797S-Mediated Resistance and Demonstrates Intracranial Activity in NSCLC.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
256 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
Abstract
purposeA secondary EGFR mutation, T790M, is the most common resistance mechanism in EGFR-mutant adenocarcinomas that have progressed on erlotinib. Third-generation EGFR inhibitors capable of inhibiting mutant EGFR with T790M produce responses in nearly two thirds of patients. However, acquired resistance mechanisms in patients treated with these drugs are yet to be described. EXPERIMENTAL
designTo study acquired resistance to third-generation EGFR inhibitors, T790M-positive cells derived from an erlotinib-resistant cancer were made resistant to a third-generation TKI and then characterized using cell and molecular analyses.
resultsCells resistant to a third-generation TKI acquired an additional EGFR mutation, C797S, which prevented suppression of EGFR. Our results demonstrate that the allelic context in which C797S was acquired may predict responsiveness to alternative treatments. If the C797S and T790M mutations are in trans, cells will be resistant to third-generation EGFR TKIs, but will be sensitive to a combination of first- and third-generation TKIs. If the mutations are in cis, no EGFR TKIs alone or in combination can suppress activity. If C797S develops in cells wild-type for T790 (when third-generation TKIs are administered in the first-line setting), the cells are resistant to third-generation TKIs, but retain sensitivity to first-generation TKIs.
conclusionsMutation of C797S in EGFR is a novel mechanism of acquired resistance to third-generation TKIs. The context in which the C797S develops with respect to the other EGFR alleles affects the efficacy of subsequent treatments.
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