Association of epidermal growth factor receptor mutations in lung cancer with chemosensitivity to gefitinib in isolated cancer cells from Japanese patients.
Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are reported to be associated with clinical responsiveness of lung cancer to gefitinib, an EGFR tyrosine kinase inhibitor. To elucidate the association between somatic mutations and the pharmacological actions of gefitinib, the chemosensitivity of isolated cancer cells from the lungs of Japanese patients to gefitinib was examined by the collagen gel-droplet embedded culture drug sensitivity test in vitro. In 30 specimens isolated from non-small-cell lung cancer patients, mutations were observed in eight tumour specimens (27%) and chemosensitivity to gefitinib was observed in seven specimens (23%). However, somatic mutations were not predominantly associated with chemosensitivity to gefitinib in vitro. Both mutation and chemosensitivity frequencies in this study were higher than those reported in studies from the United States, indicating a possible ethnic difference. Moreover, both frequencies were much higher in females than in males. Since a gender difference in chemosensitivity to gefitinib was observed in isolated cancer cells in vitro, this suggests that gefitinib works in part through the suppression of EGFR signalling, but that other factors, including sex-related factors, may participate in gefitinib action.
Nakatani
K
K
Department of Molecular and Laboratory Medicine, Mie University Graduate School of Medicine, Mie, Japan. nakatani@clin.medic.mie-u.ac.jp
Takao
M
M
Nishioka
J
J
Yasuda
K
K
Noma
K
K
Hayashi
A
A
Wada
H
H
Nobori
T
T
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011799:Quinazolines / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib