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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adenocarcinoma / drug therapy
-
Adenocarcinoma / genetics
-
Adenocarcinoma / metabolism
-
Amino Acid Motifs
-
Amino Acid Sequence
-
Amino Acid Substitution
-
Antineoplastic Agents / pharmacology
-
Antineoplastic Agents / therapeutic use
-
Carcinoma, Non-Small-Cell Lung / drug therapy
-
Carcinoma, Non-Small-Cell Lung / genetics*
-
Carcinoma, Non-Small-Cell Lung / metabolism
-
Cell Line, Tumor
-
Controlled Clinical Trials as Topic
-
Enzyme Inhibitors / pharmacology
-
Enzyme Inhibitors / therapeutic use
-
ErbB Receptors / antagonists & inhibitors*
-
ErbB Receptors / chemistry
-
ErbB Receptors / genetics
-
ErbB Receptors / metabolism
-
Female
-
Gefitinib
-
Genes, erbB-1*
-
Humans
-
Japan
-
Lung Neoplasms / drug therapy
-
Lung Neoplasms / genetics*
-
Lung Neoplasms / metabolism
-
Male
-
Molecular Sequence Data
-
Mutation*
-
Mutation, Missense
-
Phosphorylation
-
Protein Conformation
-
Protein Structure, Tertiary
-
Quinazolines / pharmacology
-
Quinazolines / therapeutic use*
-
Sequence Deletion
-
Treatment Outcome
-
United States
Substances
-
Antineoplastic Agents
-
Enzyme Inhibitors
-
Quinazolines
-
ErbB Receptors
-
Gefitinib