The article discusses the case of a patient with advanced non-small-cell lung cancer who initially responded to gefitinib, an anilinoquinazoline EGFR inhibitor. After two years of complete remission, the patient experienced a relapse, and a second mutation in the EGFR gene was identified. This mutation, a threonine-to-methionine change at position 790 (T790M), was found to confer resistance to gefitinib. Structural modeling and biochemical studies confirmed that this mutation interferes with the binding of gefitinib and other similar inhibitors, leading to drug resistance. The findings highlight the need for repeated biopsies in clinical studies to identify mutations that may lead to resistance and guide the selection of second-line treatments. The study also suggests that alternative EGFR inhibitors or targets downstream of EGFR may be necessary for patients with acquired resistance to anilinoquinazoline inhibitors.The article discusses the case of a patient with advanced non-small-cell lung cancer who initially responded to gefitinib, an anilinoquinazoline EGFR inhibitor. After two years of complete remission, the patient experienced a relapse, and a second mutation in the EGFR gene was identified. This mutation, a threonine-to-methionine change at position 790 (T790M), was found to confer resistance to gefitinib. Structural modeling and biochemical studies confirmed that this mutation interferes with the binding of gefitinib and other similar inhibitors, leading to drug resistance. The findings highlight the need for repeated biopsies in clinical studies to identify mutations that may lead to resistance and guide the selection of second-line treatments. The study also suggests that alternative EGFR inhibitors or targets downstream of EGFR may be necessary for patients with acquired resistance to anilinoquinazoline inhibitors.