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Opinion|Videos|March 13, 2026

Resistance mechanisms in EGFR-Mutated NSCLC

Author(s)Natalie I. U. Vokes, MD, Sid Devarakonda, MBBS, MD

Natalie Vokes, MD, and Sid Devarakonda, MBBS, MD, discuss resistance mechanisms in EGFR-mutated NSCLC.

Episodes in this series

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EP. 1 Risk Factors That Help Inform Treatment Selection in Frontline EGFR-Mutated NSCLC

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EP. 2 Sequencing Considerations in Advanced EGFR-Mutated NSCLC

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EP. 3 Evolving Frontline Treatment Options in EGFR-Mutated NSCLC

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EP. 4 Resistance mechanisms in EGFR-Mutated NSCLC

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EP. 5 Experiences With ADCs in EGFR-Mutated NSCLC Management

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EP. 6 Remaining Evidence Gaps in EGFR-Mutated NSCLC Care

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EP. 7 Ongoing Research to Watch in EGFR-Mutated NSCLC

Natalie Vokes, MD, and Sid Devarakonda, MBBS, MD, review both on-target and off-target resistance mechanisms that emerge during EGFR-directed therapy in EGFR-mutated NSCLC. Vokes explains how secondary EGFR mutations, MET amplification, and histologic transformation contribute to therapeutic failure. Devarakonda discusses the clinical importance of comprehensive molecular profiling to guide subsequent treatment selection.

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