EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy

Author: Paez, J. Guillermo; Janne, Pasi A.; Lee, Jeffrey C.; Tracy, Sean; Greulich, Heidi; Gabriel, Stacey; Herman, Paula; Kaye, Frederic J.; Lindeman, Neal; Boggon, Titus J.; Naoki, Katsuhiko; Sasaki, Hidefumi; Fujii, Yoshitaka; Eck, Michael J.; Sellers, William R.; Johnson, Bruce E.; Meyerson, Matthew

Description: 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 15 of 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.

Subject headings: Adenocarcinoma; Amino Acid Motifs; Amino Acid Sequence; Amino Acid Substitution; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Cell Line; Tumor; Controlled Clinical Trials as Topic; Enzyme Inhibitors; ErbB Receptors; Female; Gefitinib; Genes; erbB-1; Humans; Japan; Lung Neoplasms; Male; Molecular Sequence Data, Mutation; Mutation, Missense; Phosphorylation; Protein Conformation; Protein Structure, Tertiary; Quinazolines; Sequence Deletion; Treatment Outcome; United States; Lung cancer

Publication year: 2004

Journal or book title: Science

Volume: 304

Issue: 5676

Pages: 1497-1500

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Serial number: 3927