Mechanism of Drug Tolerant Persister Cancer Cells: The Landscape and Clinical Implication for Therapy

Abstract

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.

Keywords: Chemotherapy; Drug persisters; Drug resistance; EGFR TKI; Targeted therapy; Tumor dormancy.