[Molecular targeted therapy and tailor-made therapy for lung cancer].
Somatically acquired mutations in the epidermal growth factor receptor (EGFR) gene in lung cancer are associated with significant clinical responses to gefitinib, a tyrosine kinase inhibitor (TKI) that targets EGFR. In our previous report, 42.2% of adenocarcinoma patients has EGFR mutations, and these mutations were more frequently found in women than in men, in well differentiated tumors than poorly differentiated tumors, and in patients who were never smokers than in patients who were current/former smokers. Retrospectively, we screened the EGFR gene of tumors in 37 NSCLC patients who had been treated with gefitinib. EGFR mutations were found in 22 patients. Gefitinib was effective (CR/PR) in 15 of 22 (68.2%) patients with mutations compared with none of 15 patients without mutations. Patients with EGFR mutations survived for a longer period than without the mutations after initiation of gefitinib treatment (p = 0.0005). Gefitinib was not effective in 3 patients with K-ras mutations. Three of 4 tumors obtained from patients with acquired resistant to gefitinib, had a secondary T790M mutation. No T790M mutation was detected in pretreatment tumors. Molecular targeted therapy using TKI indicates an effective therapy specifically in lung cancer patients with EGFR mutations, and analyses of mechanisms of resistance to TKI are necessary for establishment of tailor-made therapy.
Sugio
Kenji
K
Second Department of Surgery, University of Occupational and Environmental Health, Kitakyushu, Japan.
Uramoto
H
H
Takenoyama
M
M
Hanagiri
T
T
Yasumoto
K
K
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D005260:Female; D000077156:Gefitinib; D018773:Genes, erbB-1; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000008:administration & dosage*; D012189:Retrospective Studies
D000970:Antineoplastic Agents; D011799:Quinazolines; D011505:Protein-Tyrosine Kinases; D000077156:Gefitinib