期刊
CANCER CELL
卷 37, 期 1, 页码 104-+出版社
CELL PRESS
DOI: 10.1016/j.ccell.2019.12.006
关键词
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资金
- NCI Cancer Center Support Grant [NIH 5 P30 CA06516]
- Cancer Center Support Grant at NYU Langone's Laura and Isaac Perlmutter Cancer Center [P30CA016087]
- National Cancer Institute [R01CA135257, R35CA220497]
- American Cancer Society [CRP-17-111-01-CDD]
- Claudia Adams Barr Program for Innovative Cancer Research
- Ildiko Medve and Adria Sai-Halasz EGFR Lung Cancer Research Fund
- Balassiano Family Fund for Lung Cancer Research
- Jane and Aatos Erkko Foundation
- Instrumentarium Science Foundation
- Orion Research Foundation
- Swiss Cancer League [KLS-3625-02 2015]
- Swiss National Science Foundation, Swizerland [P300PB_161026/1, P400PM_183862]
- NIH [R01 CA222218, CA233800]
- Swiss National Science Foundation (SNF) [P300PB_161026, P400PM_183862] Funding Source: Swiss National Science Foundation (SNF)
Eradicating tumor dormancy that develops following epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment of EGFR-mutant non-small cell lung cancer, is an attractive therapeutic strategy but the mechanisms governing this process are poorly understood. Blockade of ERK1/2 reactivation following EGFR TKI treatment by combined EGFR/MEK inhibition uncovers cells that survive by entering a senescence-like dormant state characterized by high YAP/TEAD activity. YAP/TEAD engage the epithelial-to-mesenchymal transition transcription factor SLUG to directly repress pro-apoptotic BMF, limiting drug-induced apoptosis. Pharmacological co-inhibition of YAP and TEAD, or genetic deletion of YAP1, all deplete dormant cells by enhancing EGFR/MEK inhibition-induced apoptosis. Enhancing the initial efficacy of targeted therapies could ultimately lead to prolonged treatment responses in cancer patients.
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