Cancer Cell Dormancy and Chemotherapy Resistance

Cancer cell dormancy is associated with tumor recurrence and metastasis. Chemotherapy usually induces dormancy as external pressure on the tumor. Dormant cells have considerable resistance to antitumor drugs, although they are not harmful to the host if they do not wake up. Chemotherapy induces a dormant phenotype through remodeling of the tumor microenvironment and alteration of intracellular signaling networks. Multiple adaptive mechanisms that confer drug resistance have been identified in these dormant cells, including the unfolded protein response to endoplasmic reticulum stress, metabolic reprogramming favoring oxidative phosphorylation to avoid damage from oxidative stress, and autophagy to realize the circular utilization of energy. However, dormancy is reversible. The conversion between dormancy and awakening of the tumor during chemotherapy and the recovery period after treatment is modulated by several factors, including the dose and cycle of treatment, and individual differences among patients. The direct elimination of cancer cells or permanent dormancy by chemotherapy predicts favorable outcomes. According to this theory, understanding the mechanisms of cancer dormancy and awakening under chemotherapy and improving prognosis using suitable treatment strategies requires further investigation. This review analyzed studies on cancer cell dormancy and response to chemotherapy to identify potential novel interests for future studies and probable strategies to optimize chemotherapy in clinical trials.