title: EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.
abstract: 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.
authors.affiliation: Departments of Medical Oncology and Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: J Guillermo
authors.initials: JG
authors.lastname: Paez
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Jänne
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Lee
authors.forename: Sean
authors.initials: S
authors.lastname: Tracy
authors.forename: Heidi
authors.initials: H
authors.lastname: Greulich
authors.forename: Stacey
authors.initials: S
authors.lastname: Gabriel
authors.forename: Paula
authors.initials: P
authors.lastname: Herman
authors.forename: Frederic J
authors.initials: FJ
authors.lastname: Kaye
authors.forename: Neal
authors.initials: N
authors.lastname: Lindeman
authors.forename: Titus J
authors.initials: TJ
authors.lastname: Boggon
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Naoki
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Sasaki
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujii
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Eck
authors.forename: William R
authors.initials: WR
authors.lastname: Sellers
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Johnson
authors.forename: Matthew
authors.initials: M
authors.lastname: Meyerson
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib