2020年1月3日
YAP1 mediates survival of ALK-rearranged lung cancer cells treated with alectinib via pro-apoptotic protein regulation.
Nature communications
- 巻
- 11
- 号
- 1
- 開始ページ
- 74
- 終了ページ
- 74
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/s41467-019-13771-5
- 出版者・発行元
- Springer Science and Business Media {LLC}
Despite the promising clinical efficacy of the second-generation anaplastic lymphoma kinase (ALK) inhibitor alectinib in patients with ALK-rearranged lung cancer, some tumor cells survive and eventually relapse, which may be an obstacle to achieving a cure. Limited information is currently available on the mechanisms underlying the initial survival of tumor cells against alectinib. Using patient-derived cell line models, we herein demonstrate that cancer cells survive a treatment with alectinib by activating Yes-associated protein 1 (YAP1), which mediates the expression of the anti-apoptosis factors Mcl-1 and Bcl-xL, and combinatorial inhibition against both YAP1 and ALK provides a longer tumor remission in ALK-rearranged xenografts when compared with alectinib monotherapy. These results suggest that the inhibition of YAP1 is a candidate for combinatorial therapy with ALK inhibitors to achieve complete remission in patients with ALK-rearranged lung cancer.
- リンク情報
- ID情報
-
- DOI : 10.1038/s41467-019-13771-5
- ISSN : 2041-1723
- ORCIDのPut Code : 71278827
- PubMed ID : 31900393
- PubMed Central 記事ID : PMC6941996