絞り込み

16404

広告

目標上積みの「タラノア対話」合意 (毎日新聞)

[PR] 温室ガス削減 「パリ協定」控え18年の1年間かけ実施へ 【ボン五十嵐和大】ドイツのボンで開催中の国連気候変動枠組み条約第23回締約国会議(COP23)...

  1. ドイツの温暖化会議で決議採択 - 福井新...
  2. 国内初の種類 恐竜の卵の化石を展示 山口...
  3. 温暖化、COP23大筋合意 先進国の削減...
  4. 本人望めば蘇生中止 消防庁委託研究班提言...

ニュース一覧

The activation of SRC family kinases and focal adhesion kinase with the loss of the amplified, mutated EGFR gene contributes to the resistance to afatinib, erlotinib and osimertinib in human lung cancer cells.

著者 Murakami Y , Sonoda K , Abe H , Watari K , Kusakabe D , Azuma K , Kawahara A , Akiba J , Oneyama C , Pachter JA , Sakai K , Nishio K , Kuwano M , Ono M
Oncotarget.2017 Sep 19 ; 8(41):70736-70751.
この記事をPubMed上で見るPubMedで表示
この記事をGoogle翻訳上で見る Google翻訳で開く

スターを付ける スターを付ける     (28view , 0users)

Full Text Sources

Miscellaneous

Second- and third-generation inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase activity (EGFR-TKIs) are improving the treatment of patients with non-small cell lung cancer. Here we established two sublines (BR1-8 and BR2-3) resistant to a second-generation inhibitor, afatinib, from the human lung cancer cell line HCC827 that harbors a mutation that activates the tyrosine kinase activity of EGFR. These afatinib-resistant sublines were resistant to first-generation EGFR-TKIs, gefitinib and erlotinib, and a third-generation EGFR-TKI, osimertinib. These resistant sublines showed markedly reduced levels of multiple EGFR family proteins, including the activated mutant EGFR, and complete loss of EGFR amplification as compared with their parental HCC827 cells harboring amplification of EGFR gene. Treatment with the multikinase inhibitor dasatinib or transfection with a SRC small interfering RNA inhibited cell survival and AKT phosphorylation in drug-resistant sublines to a greater extent compared with HCC827 cells. Further, the migration of drug-resistant cells was greater compared with that of HCC827 cells and was inhibited by dasatinib or an FAK inhibitor. These findings indicate that compensatory activation of SRC family kinases (SFKs) and FAK supports the survival and migration of afatinib-resistant cells when the expression of multiple EGFR family proteins was mostly abrogated. Combinations of potent drugs that target SFKs and FAK may overcome the resistance of lung cancer cells to second-generation TKIs.
PMID: 29050315 [PubMed]
印刷用ページを開く Endnote用テキストダウンロード