HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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

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.
AuthorsSusumu Kobayashi, Titus J Boggon, Tajhal Dayaram, Pasi A Jänne, Olivier Kocher, Matthew Meyerson, Bruce E Johnson, Michael J Eck, Daniel G Tenen, Balázs Halmos
JournalThe New England journal of medicine (N Engl J Med) Vol. 352 Issue 8 Pg. 786-92 (Feb 24 2005) ISSN: 1533-4406 [Electronic] United States
PMID15728811 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
CopyrightCopyright 2005 Massachusetts Medical Society.
Chemical References
  • Antineoplastic Agents
  • DNA, Neoplasm
  • Quinazolines
  • RNA, Neoplasm
  • Erlotinib Hydrochloride
  • ErbB Receptors
  • Gefitinib
Topics
  • Aged
  • Antineoplastic Agents (adverse effects, therapeutic use)
  • Biopsy
  • Carcinoma, Non-Small-Cell Lung (diagnosis, drug therapy, genetics)
  • DNA, Neoplasm
  • Drug Resistance, Neoplasm (genetics)
  • ErbB Receptors (antagonists & inhibitors, chemistry, genetics)
  • Erlotinib Hydrochloride
  • Gefitinib
  • Humans
  • Lung Neoplasms (diagnosis, drug therapy, genetics)
  • Male
  • Models, Structural
  • Molecular Structure
  • Neoplasm Recurrence, Local (pathology)
  • Point Mutation
  • Quinazolines (adverse effects, chemistry, metabolism, therapeutic use)
  • RNA, Neoplasm
  • Sequence Analysis, DNA
  • Sequence Analysis, RNA

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: