Fig. 1.

Mechanisms underlying maintenance and awakening of dormant cancer cells. Cancer dormancy is classified as tumor mass dormancy and cellular dormancy. Tumor mass dormancy is the equilibrium between cell proliferation and cell death, which is regulated by blood supply and the immune system. Cellular dormancy is the status of reversible growth arrest and characterized by cell cycle arrest at the G0/G1 phase of the cell cycle, induction of CDK inhibitors, reduction of proliferation markers (such as Ki67 and PCNA), p38 MAPK activation, compacted chromatin structure, and reduction of cellular metabolism. Several mechanisms, such as autophagy, stress-tolerance signaling, microenvironmental cues, and epigenetic modifications, are involved in the maintenance of cellular dormancy. Dormant cancer cells escape from the dormant status via changing autocrine soluble factors autonomously and/or interacting with surrounding stromal cells in the microenvironments. CDK, cyclin-dependent kinase; MAPK, mitogen-activated protein kinase; PCNA, proliferating cell nuclear antigen.