期刊
JOURNAL OF THORACIC ONCOLOGY
卷 16, 期 11, 页码 1798-1809出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jtho.2021.07.017
关键词
Drug persisters; Targeted therapy; EGFR TKI; Chemotherapy; Tumor dormancy; Drug resistance
资金
- Canadian Institutes of Health Research Foundation [FDN-1483953]
- Princess Margaret Cancer Foundation
- Terry Fox Foundation Training Program in Molecular Pathology of Cancer Transitional grant
- Princess Margaret Cancer Foundation matching grant
- Saitama Medical School, Japan
- Lusi Wong Family Fund
A minor population of cancer cells can evade cell death from chemotherapy and targeted therapy by entering a reversible slow proliferation state known as the drug tolerant persister (DTP) state. Understanding the biology of DTP cells and developing therapeutic strategies targeting this mechanism can have significant clinical implications in overcoming cancer persistence. Emerging evidence suggests that DTP cells adapt to new environments through epigenomic modification, transcriptomic regulation, flexible energy metabolism, and interactions with the tumor microenvironment.
A minor population of cancer cells may evade cell death from chemotherapy and targeted therapy by entering a reversible slow proliferation state known as the drug tolerant persister (DTP) state. This DTP state can allow cancer cells to survive drug therapy long enough for additional mechanisms of acquired drug resistance to develop. Thus, cancer persistence is a major obstacle to curing cancers, where insight into the biology of DTP cells and therapeutic strategies targeting this mechanism can have considerable clinical implications. There is emerging evidence that DTP cells adapt to new environments through epigenomic modification, transcriptomic regulation, flexible energy metabolism, and interactions with the tumor microenvironment. Herein, we review and discuss the various proposed mechanisms of cancer persister cells and the molecular features underlying the DTP state, with insights into the potential therapeutic strategies to conquer DTP cells and prevent cancer recurrence or therapeutic failures. (c) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
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