EGFR mutation and resistance of non-small-cell lung cancer to gefitinib

Mutations of the epidermal growth factor receptor ( EGFR) gene have been identified in from patients with non-small-cell lung cancer who have a response to anilinoquinazoline EGFR inhibitors. Despite the dramatic responses to such inhibitors, patients ultimately have a relapse. The mechanism of the drug resistance is unknown. Here we report the case of a patient with EGFR - mutant, gefitinib-responsive, non-small-cell lung cancer who had a relapse after two years of complete remission during treatment with gefitinib. The DNA sequence of the EGFR gene in his biopsy specimen at relapse revealed the presence of a second point mutation, resulting in threonine-to-methionine amino acid change at position 790 of EGFR. Structural modeling and biochemical studies showed that this second mutation led to gefitinib resistance.