Receptor ligand-triggered resistance to alectinib and its circumvention by Hsp90 inhibition in EML4-ALK lung cancer cells

Receptor ligand-triggered resistance to alectinib and its circumvention by Hsp90 inhibition in EML4-ALK lung cancer cells

フォーマット:

論文

責任表示:

Tanimoto, Azusa ; Yamada, Tadaaki ; Nanjo, Shigeki ; Takeuchi, Shinji ; Ebi, Hiromichi ; Kita, Kenji ; Matsumoto, Kunio ; Yano, Seiji

言語:

英語

出版情報:

Impact Journals LLC, 2014-01-01

著者名:

掲載情報:

Oncotarget

ISSN:

1949-2553

巻:

5

通号:

13

開始ページ:

4920

終了ページ:

4928

バージョン:

publisher

概要:

Alectinib is a new generation ALK inhibitor with activity against the gatekeeper L1196M mutation that showed remarkable activity in a phase I/II study with echinoderm microtubule associated protein-like 4 (EML4) - anaplastic lymphoma kinase (ALK) non-small cell lung cancer (NSCLC) patients. However, alectinib resistance may eventually develop. Here, we found that EGFR ligands and HGF, a ligand of the MET receptor, activate EGFR and MET, respectively, as alternative … pathways, and thereby induce resistance to alectinib. Additionally, the heat shock protein 90 (Hsp90) inhibitor suppressed protein expression of ALK, MET, EGFR, and AKT, and thereby induced apoptosis in EML4-ALK NSCLC cells, even in the presence of EGFR ligands or HGF. These results suggest that Hsp90 inhibitors may overcome ligand-triggered resistance to new generation ALK inhibitors and may result in more successful treatment of NSCLC patients with EML4-ALK. 続きを見る

URL:

http://hdl.handle.net/2297/45905

タイトル・著者・出版者が同じ資料

詳細

主題:	Drug resistance; EML4-ALK; Hsp90 inhibitor; New generation ALK inhibitor; Receptor ligands
受理日:	2014-01-01

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1 学位論文 Receptor ligand-triggered resistance to alectinib and its circumvention by Hsp90 inhibition in EML4-ALK lung cancer cells 谷本, 梓, Tanimoto, Azusa	7 論文 Ligand-triggered resistance to molecular targeted drugs in lung cancer: Roles of hepatocyte growth factor and epidermal growth factor receptor ligands Yano, Seiji, Takeuchi, Shinji, Nakagawa, Takayuki, Yamada, Tadaaki Japanese Cancer Association / Blackwell Publishing Ltd
2 学位論文 Receptor ligand-triggered resistance to alectinib and its circumvention by Hsp90 inhibition in EML4-ALK lung cancer cells 谷本, 梓, Tanimoto, Azusa	8 論文 Met Kinase Inhibitor E7050 Reverses Three Different Mechanisms of Hepatocyte Growth Factor-induced Tyrosine Kinase Inhibitor Resistance in EGFR Mutant Lung … Wang, Wei, Li, Qi, Takeuchi, Shinji, Yamada, Tadaaki, Koizumi, Hitomi, Nakamura, Takahiro, Matsumoto, Kunio, Mukaida, …
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