Regulating the dormancy of cancer stem cells: a novel approach to preventing cancer relapse

Dormant cancer stem cells (CSCs) are the root cause of the drug resistance and metastatic processes of malignant tumors, but an in-depth analysis of their biological mechanisms is needed. Dormant CSCs are in the G0 phase of the cell cycle and are characterized by enhanced autophagic activity, a stable genomic structure and strong plasticity. Recently, several new specific markers of dormant CSCs, such as p27, CD13, QSOX1, Survivin, GPD1 and BEX2, have been identified, which offer hope for targeted therapy. In addition, epigenetic modifications such as DNA methylation and histone modifications have been reported to regulate the transition between the quiescent and proliferative states of dormant CSCs. From a clinical perspective, keeping cancer stem cells in a dormant state is helpful for preventing tumor recurrence and metastasis. To this end, clarifying the potential mechanisms and molecular regulation of cancer stem cell dormancy is vital. Here, in this review, we examine recent significant findings regarding tumor stem cell dormancy in both experimental and human disease models, emphasizing the underlying molecular mechanisms, regulatory processes, experimental models, and prospective research directions aimed at advancing this field and enhancing clinical translation.