PMID- 19680293
OWN - NLM
STAT- MEDLINE
DCOM- 20090910
LR  - 20220409
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 28 Suppl 1
IP  - Suppl 1
DP  - 2009 Aug
TI  - Activating and resistance mutations of EGFR in non-small-cell lung cancer: role 
      in clinical response to EGFR tyrosine kinase inhibitors.
PG  - S24-31
LID - 10.1038/onc.2009.198 [doi]
AB  - The epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), 
      gefitinib and erlotinib, are reversible competitive inhibitors of the tyrosine 
      kinase domain of EGFR that bind to its adenosine-5' triphosphate-binding site. 
      Somatic activating mutations of the EGFR gene, increased gene copy number and 
      certain clinical and pathological features have been associated with dramatic 
      tumor responses and favorable clinical outcomes with these agents in patients 
      with non-small-cell lung cancer (NSCLC). The specific types of activating 
      mutations that confer sensitivity to EGFR TKIs are present in the tyrosine kinase 
      (TK) domain of the EGFR gene. Exon 19 deletion mutations and the single-point 
      substitution mutation L858R in exon 21 are the most frequent in NSCLC and are 
      termed 'classical' mutations. The NSCLC tumors insensitive to EGFR TKIs include 
      those driven by the KRAS and MET oncogenes. Most patients who initially respond 
      to gefitinib and erlotinib eventually become resistant and experience progressive 
      disease. The point mutation T790M accounts for about one half of these cases of 
      acquired resistance. Various second-generation EGFR TKIs are currently being 
      evaluated and may have the potential to overcome T790M-mediated resistance by 
      virtue of their irreversible inhibition of the receptor TK domain.
FAU - Gazdar, A F
AU  - Gazdar AF
AD  - Hamon Center for Therapeutic Oncology Research and Department of Pathology, 
      University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. 
      adi.gazdar@utsouthwestern.edu
LA  - eng
GR  - P50 CA070907/CA/NCI NIH HHS/United States
GR  - P50 CA070907-109001/CA/NCI NIH HHS/United States
GR  - P50CA70907/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (KRAS protein, human)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Quinazolines)
RN  - 0 (Receptors, Growth Factor)
RN  - DA87705X9K (Erlotinib Hydrochloride)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (MET protein, human)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
RN  - EC 3.6.5.2 (ras Proteins)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics
MH  - Drug Resistance, Neoplasm/*genetics
MH  - ErbB Receptors/antagonists & inhibitors/*genetics
MH  - Erlotinib Hydrochloride
MH  - Gefitinib
MH  - Gene Amplification
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/genetics
MH  - *Point Mutation
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Protein Structure, Tertiary/drug effects
MH  - Proto-Oncogene Proteins/genetics
MH  - Proto-Oncogene Proteins c-met
MH  - Proto-Oncogene Proteins p21(ras)
MH  - Quinazolines/therapeutic use
MH  - Receptors, Growth Factor/genetics
MH  - Sequence Deletion
MH  - Treatment Outcome
MH  - ras Proteins/genetics
PMC - PMC2849651
MID - NIHMS148095
EDAT- 2009/08/15 09:00
MHDA- 2009/09/11 06:00
PMCR- 2010/04/05
CRDT- 2009/08/15 09:00
PHST- 2009/08/15 09:00 [entrez]
PHST- 2009/08/15 09:00 [pubmed]
PHST- 2009/09/11 06:00 [medline]
PHST- 2010/04/05 00:00 [pmc-release]
AID - onc2009198 [pii]
AID - 10.1038/onc.2009.198 [doi]
PST - ppublish
SO  - Oncogene. 2009 Aug;28 Suppl 1(Suppl 1):S24-31. doi: 10.1038/onc.2009.198.