Cellular Dormancy in Cancer: Mechanisms and Potential Targeting Strategies

Abstract

Cancer is a leading cause of disease-related mortality worldwide. Drug resistance is one of the primary reasons for the failure of anticancer therapy. There are a number of underlying mechanisms for anticancer drug resistance including genetic/epigenetic modifications, microenvironmental factors, and tumor heterogeneity. In the present scenario, researchers have focused on these novel mechanisms and strategies to tackle them. Recently, researchers have recognized the ability of cancer to become dormant because of anticancer drug resistance, tumor relapse, and progression. Currently, cancer dormancy is classified into "tumor mass dormancy" and "cellular dormancy." Tumor mass dormancy represents the equilibrium between cell proliferation and cell death under the control of blood supply and immune responses. Cellular dormancy denotes the state in which cells undergo quiescence and is characterized by autophagy, stress-tolerance signaling, microenvironmental cues, and epigenetic modifications. Cancer dormancy has been regarded as the stem of primary or distal recurrent tumor formation and poor clinical outcomes in cancer patients. Despite the insufficiency of reliable models of cellular dormancy, the mechanisms underlying the regulation of cellular dormancy have been clarified in numerous studies. A better understanding of the biology of cancer dormancy is critical for the development of effective anticancer therapeutic strategies. In this review, we summarize the characteristics and regulatory mechanisms of cellular dormancy, introduce several potential strategies for targeting cellular dormancy, and discuss future perspectives.

Persister cancer cells are characterized by H4K20me3 heterochromatin that defines a low inflammatory profile

“…Among the common traits between senescent and persister/diapause-like cancer cells is the expansion of the lysosomal compartment, which is likely attributable to an increased autophagic activity 11,75 . Interestingly, the senescence-associated -galactosidase activity (SA--GAL) which is a lysosomal enzyme detected at a sub-optimal pH in senescent cells was absent persister cells, therefore disconnecting lysosomal expansion from SA--GAL.…”

Tumor Dormancy and Reactivation: The Role of Heat Shock Proteins

“…Dormant tumor cells arise from DTCs of extravasated early-seeder circulating tumor cells (CTCs). Apart from their growth reversibility capacity, dormant tumor cells have a decreased metabolic state and an altered chromatin and epigenetic structure at the molecular and sub-molecular levels, which facilitates their prolonged period of dormancy [17][18][19].…”

Unveiling the role of cellular dormancy in cancer progression and recurrence

“…Growing evidence points to the emergence of dormant cells as a contributor to the disease's aptitude to evade therapeutic interventions [2,3 ▪ ,4,5,6 ▪ ]. In this context, cellular dormancy refers to cells entering a prolonged state of reduced proliferation, where growth is considerably slowed down or halted [7 ▪ ,8]. This concept overlaps largely with other programs of proliferative arrest, specifically quiescence (i.e.…”

“…Cellular dormancy is an evolutionarily conserved adaptation, typically employed by stem and progenitor cells in-between bursts of proliferative phases [7 ▪ ]. As described in 1954, malignant cells can spontaneously enter dormancy, explaining the latency between cancer dissemination and clinical relapse, often spanning years [14].…”