[HTML][HTML] EGFR Mutation and Resistance of Non–Small-Cell Lung Cancer to Gefitinib

S Kobayashi, TJ Boggon, T Dayaram… - … England Journal of …, 2005 - Mass Medical Soc
S Kobayashi, TJ Boggon, T Dayaram, PA Jänne, O Kocher, M Meyerson, BE Johnson…
New England Journal of Medicine, 2005Mass Medical Soc
Mutations of the epidermal growth factor receptor (EGFR) gene have been identified in
specimens from patients with non–small-cell lung cancer who have a response to
anilinoquinazoline EGFR inhibitors. Despite the dramatic responses to such inhibitors, most
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, advanced non–small-
cell lung cancer who had a relapse after two years of complete remission during treatment …
Mutations of the epidermal growth factor receptor (EGFR) gene have been identified in specimens from patients with non–small-cell lung cancer who have a response to anilinoquinazoline EGFR inhibitors. Despite the dramatic responses to such inhibitors, most 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, advanced 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 tumor 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.
The New England Journal Of Medicine