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.
|
Authors | 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 |
Journal | The 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 |
PMID | 15728811
(Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
Copyright | Copyright 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
|