| アイテムタイプ |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2024-12-05 |
| タイトル |
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|
タイトル |
Pan‐HER inhibitors overcome lorlatinib resistance caused by NRG1/HER3 activation in ALK‐rearranged lung cancer |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
ALK inhibitor |
| キーワード |
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|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
drug resistance |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
HER3 |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
lorlatinib |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
non–small‐cell lung cancer |
| 資源タイプ |
|
|
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 |
| 著者 |
Taniguchi, Hirokazu
Akagi, Kazumasa
Dotsu, Yosuke
Yamada, Tadaaki
Ono, Sawana
Imamura, Erika
Gyotoku, Hiroshi
Takemoto, Shinnosuke
Yamaguchi, Hiroyuki
Sen, Triparna
Yano, Seiji
Mukae, Hiroshi
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| 抄録 |
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内容記述タイプ |
Abstract |
|
内容記述 |
Lorlatinib, a third‐generation anaplastic lymphoma kinase (ALK)‐tyrosine kinase inhibitor (TKI) with a broad coverage against ALK mutations, has demonstrated dramatic effects in patients with ALK‐rearranged lung cancer. The mechanisms of acquired resistance to lorlatinib by secondary ALK compound mutations have recently been reported; however, resistance mechanisms other than secondary mutations remain unclear. Here, we investigated the molecular mechanisms of the acquired resistance in ALK‐rearranged lung cancer cells in vitro. We established two different lorlatinib‐resistant ALK‐rearranged lung cancer cell lines (H3122LR and A925LLR) via long‐term administration of lorlatinib. These resistant cells did not harbor the secondary ALK mutations and showed cross‐resistance to the other kinds of ALK‐TKIs (crizotinib or alectinib) compared with the parental cells; however, these resistant cells overexpressed the phosphorylated human epidermal growth factor receptor 3 (HER3) protein and the ligand of HER3 (neuregulin 1; NRG1). Pharmacological inhibition of HER3 with pan‐HER inhibitors or genetic knockdown of HER3 with siRNA resensitized H3122LR and A925LLR cells to lorlatinib in vitro, indicating that H3122LR and A925LLR acquired resistance by NRG1/HER3 activation. These findings demonstrated that targeting NRG1/HER3 is a potential novel therapeutic option for lorlatinib‐resistant ALK‐rearranged lung cancer. |
|
言語 |
en |
| 書誌情報 |
en : Cancer Science
巻 114,
号 1,
p. 164-173,
発行日 2022-09-06
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| 出版者 |
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出版者 |
John Wiley & Sons, Ltd |
|
言語 |
en |
| 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 |
1347-9032 |
| DOI |
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|
関連タイプ |
isIdenticalTo |
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|
識別子タイプ |
DOI |
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|
関連識別子 |
10.1111/cas.15579 |
| 権利 |
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|
権利情報 |
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association |
|
言語 |
en |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 引用 |
|
|
内容記述タイプ |
Other |
|
内容記述 |
Cancer Science, 114(1), pp.164-173; 2022 |
|
言語 |
en |
CS114_164.pdf (9.5 MB)
