PMID- 15728811
OWN - NLM
STAT- MEDLINE
DCOM- 20050228
LR  - 20240104
IS  - 1533-4406 (Electronic)
IS  - 0028-4793 (Linking)
VI  - 352
IP  - 8
DP  - 2005 Feb 24
TI  - EGFR mutation and resistance of non-small-cell lung cancer to gefitinib.
PG  - 786-92
AB  - 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.
CI  - Copyright 2005 Massachusetts Medical Society.
FAU - Kobayashi, Susumu
AU  - Kobayashi S
AD  - Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard 
      Medical School, Boston, USA.
FAU - Boggon, Titus J
AU  - Boggon TJ
FAU - Dayaram, Tajhal
AU  - Dayaram T
FAU - Janne, Pasi A
AU  - Janne PA
FAU - Kocher, Olivier
AU  - Kocher O
FAU - Meyerson, Matthew
AU  - Meyerson M
FAU - Johnson, Bruce E
AU  - Johnson BE
FAU - Eck, Michael J
AU  - Eck MJ
FAU - Tenen, Daniel G
AU  - Tenen DG
FAU - Halmos, Balazs
AU  - Halmos B
LA  - eng
GR  - 1K12CA87723-01/CA/NCI NIH HHS/United States
GR  - PA20-CA090578-01A1/CA/NCI NIH HHS/United States
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - N Engl J Med
JT  - The New England journal of medicine
JID - 0255562
RN  - 0 (Antineoplastic Agents)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Quinazolines)
RN  - 0 (RNA, Neoplasm)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - S65743JHBS (Gefitinib)
SB  - IM
CIN - N Engl J Med. 2005 Feb 24;352(8):830-2. PMID: 15728818
CIN - N Engl J Med. 2005 May 19;352(20):2136; author reply 2136. PMID: 15901872
CIN - Nat Clin Pract Oncol. 2005 Jun;2(6):296-7. PMID: 16264986
MH  - Aged
MH  - Antineoplastic Agents/adverse effects/*therapeutic use
MH  - Biopsy
MH  - Carcinoma, Non-Small-Cell Lung/diagnosis/drug therapy/*genetics
MH  - DNA, Neoplasm
MH  - Drug Resistance, Neoplasm/*genetics
MH  - ErbB Receptors/*antagonists & inhibitors/chemistry/*genetics
MH  - Erlotinib Hydrochloride
MH  - Gefitinib
MH  - Humans
MH  - Lung Neoplasms/diagnosis/drug therapy/*genetics
MH  - Male
MH  - Models, Structural
MH  - Molecular Structure
MH  - Neoplasm Recurrence, Local/pathology
MH  - Point Mutation
MH  - Quinazolines/adverse effects/chemistry/metabolism/*therapeutic use
MH  - RNA, Neoplasm
MH  - Sequence Analysis, DNA
MH  - Sequence Analysis, RNA
EDAT- 2005/02/25 09:00
MHDA- 2005/03/01 09:00
CRDT- 2005/02/25 09:00
PHST- 2005/02/25 09:00 [pubmed]
PHST- 2005/03/01 09:00 [medline]
PHST- 2005/02/25 09:00 [entrez]
AID - 352/8/786 [pii]
AID - 10.1056/NEJMoa044238 [doi]
PST - ppublish
SO  - N Engl J Med. 2005 Feb 24;352(8):786-92. doi: 10.1056/NEJMoa044238.