title: Non-responsiveness to gefitinib in a patient with lung adenocarcinoma having rare EGFR mutations S768I and V769L.
abstract: Mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) are associated with clinical responsiveness to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small cell lung cancers (NSCLCs). However, certain rare EGFR mutations including S768I are reported to confer less in vitro sensitivity to gefitinib, an EGFR-TKI, than major mutations such as exon 19 deletions and L858R and even the wild-type counterpart. Here, we report the first case of adenocarcinoma of the lung in which the patient had rare mutations S768I and V769L and was treated with gefitinib. Disease progressed during 6 weeks of treatment. This case suggests that in vitro sensitivity to gefitinib correlates with distinct clinical responsiveness to gefitinib in various types of EGFR mutations.
authors.affiliation: First Department of Medicine, Hokkaido University School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan. hajime.asahina@nifty.ne.jp <hajime.asahina@nifty.ne.jp>
authors.forename: Hajime
authors.initials: H
authors.lastname: Asahina
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamazaki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kinoshita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yokouchi
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Dosaka-Akita
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000032:analysis; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D000077156:Gefitinib; D006801:Humans; D007532:Isoleucine / Q000737:chemistry / Q000235:genetics; D007930:Leucine / Q000737:chemistry / Q000235:genetics; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011799:Quinazolines / Q000627:therapeutic use*; D012694:Serine / Q000737:chemistry / Q000235:genetics; D014633:Valine / Q000737:chemistry / Q000235:genetics
chemical_list: D004273:DNA, Neoplasm; D011799:Quinazolines; D007532:Isoleucine; D012694:Serine; D066246:ErbB Receptors; D007930:Leucine; D014633:Valine; D000077156:Gefitinib