アリヤマ　トモヒロ   Ariyama Tomohiro   有山　智博    所属   東邦大学  薬学部 薬学科    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Comparative Study of Different Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitors Affecting Lung Cancer Cell Lines Stably Overexpressing EGFR Mutations
掲載誌名	正式名：BPB Reports
掲載区分	国内
巻・号・頁	4(1),pp.12-16
著者・共著者	Tomohiro Ariyama, Yuichiro Kanno, Sonomi Takizawa, Kiyomitsu Nemoto, Toshihiro Ishii
担当区分	筆頭著者,責任著者
発行年月	2021/01/28
概要	Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are effective drugs against non-small cell lung cancer (NSCLC) cells harboring common EGFR mutations such as in-frame exon 19 deletions (Del19) and the exon 21 L858R point mutations (L858R). However, currently used EGFR-TKIs are less effective against cells showing uncommon EGFR mutations. Because there is less information available on the sensitivities of the uncommon EGFR mutations, it is important to evaluate the effect of EGFR-TKIs on uncommon mutations. In this study, we sought to establish H1299 NSCLC cell lines stably expressing mutated EGFRs having Del18, G719S, or L861Q that are uncommon mutations as well as Del19 or L858R common mutations, and evaluated whether these cell lines could be applied as a prediction system for the therapeutic effects of EGFR-TKIs. In fact, the levels of phosphorylated EGFR in these cell lines were assessed after treatment with various EGFR-TKIs (4 approved and 4 unapproved drugs). Gefitinib, erlotinib, afatinib, and osimertinib, approved drugs, were effective against Del19, L858R, and L861Q mutations. However, these EGFR-TKIs were less effective against G719S and Del18 mutations. The unapproved drugs neratinib and poziotinib were effective against Del19, L858R, Del18, and L861Q mutations. Interestingly, canertinib and sapitinib had effects against Del19, Del18, and L861Q mutations and no effect against L858R mutation. These results indicate that the established cell lines are suitable for assessing the effects of the EGFR-TKIs on EGFR mutations, including uncommon mutations, and that some of the EGFR-TKIs used are also effective against uncommon mutations.