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

Susumu Kobayashi, Titus J. Boggon, Tajhal Dayaram, Pasi A. Jänne, Olivier Kocher, Matthew Meyerson, Bruce E. Johnson, Michael J. Eck, Daniel G. Tenen, Balázs Halmos

Research output: Contribution to journalArticle

3030 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)786-792
Number of pages7
JournalNew England Journal of Medicine
Volume352
Issue number8
DOIs
StatePublished - Feb 24 2005
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Kobayashi, S., Boggon, T. J., Dayaram, T., Jänne, P. A., Kocher, O., Meyerson, M., Johnson, B. E., Eck, M. J., Tenen, D. G., & Halmos, B. (2005). EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. New England Journal of Medicine, 352(8), 786-792. https://doi.org/10.1056/NEJMoa044238