Circadian disruption in cancer and regulation of cancer stem cells by circadian clock genes: An updated review

Circadian rhythm, regulated by a time keeping system termed as the circadian clock, is important for many biological processes in eukaryotes. Disordered circadian rhythm is implicated in different human diseases, including cardiovascular disease, neurologic disease, metabolic disorders, and cancer. The stem like-cancer cells (or cancer stem cells, CSCs) are proposed to stand at the top of the heterogeneous hierarchy in different solid tumors, which are responsible for tumor initiation, development, therapy resistance and metastasis. Emerging evidence has shown that circadian clock genes potentially regulate the stemness and features of CSCs in several malignant systems, including leukemia, glioblastoma, breast cancer, colorectal cancer and prostate cancer. The chronotherapies targeting CSCs are therefore of therapeutic potentials in treating malignancies. In this review, we have summarized our current knowledge of circadian clock gene regulation in normal stem/progenitor cells. Moreover, we have provided evidence linking dysregulations of circadian clock genes and cancer development. Importantly, we have listed the potential mechanisms underlying circadian clock gene regulation of CSCs. Finally, we have offered the current attempts of chronotherapy targeting CSCs. Elucidating the molecular regulation of circadian clock gene in CSCs will provide us a novel direction for the development of therapeutics to target CSCs.