Resistance to gefitinib.
Subsets of patients with non-small cell lung cancer (NSCLC) who carry somatic mutations in the epidermal growth factor receptor (EGFR) have responded remarkably well to a tyrosine kinase inhibitor (TKI), gefitinib. Despite the dramatic response to this inhibitor, most patients nevertheless ultimately have a relapse. We herein report a case of advanced NSCLC in a patient carrying mutated EGFR (delE746-A750) who had a relapse after dramatic improvement by gefitinib treatment. The DNA sequence of the EGFR gene in a tumor biopsy specimen obtained from the relapse site revealed the presence of a second point mutation, resulting in a threonine-to-methionine amino acid substitution at position 790 of EGFR, which could not be detected in the tumor specimen taken before the treatment. Screening subjects with EGFR mutations therefore allows us to identify patients who can be successfully treated with gefitinib. Such observations should also help us in the search for more effective therapies against a specific subset of NSCLC.
Uramoto
Hidetaka
H
Second Department of Surgery, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
Sugio
Kenji
K
Oyama
Tsunehiro
T
Sugaya
Masakazu
M
Hanagiri
Takeshi
T
Yasumoto
Kosei
K
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D017354:Point Mutation; D011799:Quinazolines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D011799:Quinazolines; D066246:ErbB Receptors; D000077156:Gefitinib