EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.
Receptor tyrosine kinase genes were sequenced in non-small cell lung cancer (NSCLC) and matched normal tissue. Somatic mutations of the epidermal growth factor receptor gene EGFR were found in 15of 58 unselected tumors from Japan and 1 of 61 from the United States. Treatment with the EGFR kinase inhibitor gefitinib (Iressa) causes tumor regression in some patients with NSCLC, more frequently in Japan. EGFR mutations were found in additional lung cancer samples from U.S. patients who responded to gefitinib therapy and in a lung adenocarcinoma cell line that was hypersensitive to growth inhibition by gefitinib, but not in gefitinib-insensitive tumors or cell lines. These results suggest that EGFR mutations may predict sensitivity to gefitinib.
Paez
J Guillermo
JG
Departments of Medical Oncology and Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Jänne
Pasi A
PA
Lee
Jeffrey C
JC
Tracy
Sean
S
Greulich
Heidi
H
Gabriel
Stacey
S
Herman
Paula
P
Kaye
Frederic J
FJ
Lindeman
Neal
N
Boggon
Titus J
TJ
Naoki
Katsuhiko
K
Sasaki
Hidefumi
H
Fujii
Yoshitaka
Y
Eck
Michael J
MJ
Sellers
William R
WR
Johnson
Bruce E
BE
Meyerson
Matthew
M
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D018849:Controlled Clinical Trials as Topic; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D018773:Genes, erbB-1; D006801:Humans; D007564:Japan; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010766:Phosphorylation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D017384:Sequence Deletion; D016896:Treatment Outcome; D014481:United States
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib