| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2017-10-05 |
| タイトル |
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タイトル |
Met Kinase Inhibitor E7050 Reverses Three Different Mechanisms of Hepatocyte Growth Factor-induced Tyrosine Kinase Inhibitor Resistance in EGFR Mutant Lung Cancer |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| ID登録 |
|
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ID登録 |
10.24517/00027435 |
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ID登録タイプ |
JaLC |
| 著者 |
Wang, Wei
Li, Qi
Takeuchi, Shinji
Yamada, Tadaaki
Koizumi, Hitomi
Nakamura, Takahiro
松本, 邦夫
Mukaida, Naofumi
Nishioka, Yasuhiko
Sone, Saburo
Nakagawa, Takayuki
Uenaka, Toshimitsu
Yano, Seiji
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| 著者別表示 |
竹内, 伸司
山田, 忠明
中村, 隆弘
松本, 邦夫
向田, 直史
西岡, 安彦
曽根, 三郎
矢野, 聖二
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| 提供者所属 |
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内容記述タイプ |
Other |
|
内容記述 |
金沢大学がん進展制御研究所 |
| 書誌情報 |
Clinical Cancer Research
巻 18,
号 6,
p. 1663-1671,
発行日 2012-03-15
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| ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
1078-0432 |
| NCID |
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収録物識別子タイプ |
NCID |
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収録物識別子 |
AA11029881 |
| DOI |
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関連タイプ |
isVersionOf |
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識別子タイプ |
DOI |
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関連識別子 |
https://doi.org/10.1158/1078-0432.ccr-11-1171 |
| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
PURPOSE: Hepatocyte growth factor (HGF) induces resistance to reversible and irreversible epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutant lung cancer cells by activating Met and the downstream PI3K/Akt pathway. Moreover, continuous exposure to HGF accelerates the emergence of EGFR-TKI-resistant clones. We assayed whether a new Met kinase inhibitor, E7050, which is currently being evaluated in clinical trials, could overcome these three mechanisms of resistance to EGFR-TKIs. EXPERIMENTAL DESIGN: The effects of E7050 on HGF-induced resistance to reversible (gefitinib), irreversible (BIBW2992), and mutant-selective (WZ4002) EGFR-TKIs were determined using the EGFR-mutant human lung cancer cell lines PC-9 and HCC827 with an exon 19 deletion, and H1975 with an T790M secondary mutation. PC-9 cells were mixed with HGF-producing fibroblasts, MRC-5 cells, and subcutaneously inoculated into SCID mice and the therapeutic effects of E7050 plus gefitinib were assayed. RESULTS: E7050 circumvented resistance to all of the reversible, irreversible, and mutant-selective EGFR-TKIs induced by exogenous and/or endogenous HGF in EGFR mutant lung cancer cell lines, by blocking the Met/Gab1/PI3K/Akt pathway in vitro. E7050 also prevented the emergence of gefitinib-resistant HCC827 cells induced by continuous exposure to HGF. In the in vivo model, E7050 plus gefitinib resulted in marked regression of tumor growth associated with inhibition of Akt phosphorylation in cancer cells. CONCLUSIONS: A new Met kinase inhibitor, E7050, reverses the three HGF-induced mechanisms of gefitinib resistance, suggesting that E7050 may overcome HGF-induced resistance to gefitinib and next-generation EGFR-TKIs. |
| 著者版フラグ |
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出版タイプ |
AM |
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出版タイプResource |
http://purl.org/coar/version/c_ab4af688f83e57aa |
| 関連URI |
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識別子タイプ |
URI |
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関連識別子 |
http://www.ncbi.nlm.nih.gov/pubmed/22317763 |
CA-PR-TAKEUCHI-S-2012.pdf (1.1 MB)
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