The circadian clock and cancer: links between circadian disruption and disease Pathology

There is growing evidence that disruption of our 24-h clock increases our risk for acquiring several diseases and disorders. One of these diseases is cancer. While the mechanistic links between circadian clock disruption and cancer initiation or progression are an active area of study, significantly more work needs to be done to understand the molecular substrates involved. Of particular complexity remains the functions of the clock in individual cells during the process of transformation (cancer initiation) versus the functions of the clock in tumour-surrounding stroma in the process of tumour progression or metastasis. Indeed, the nexus of cellular circadian dynamics, metabolism and carcinogenesis is drawing more attention, and many new studies are now highlighting the critical role of circadian rhythms and clock proteins in cancer prevention. In this brief review, we cover some of the basic mechanisms reported to link circadian disruption and cancer at the level of gene expression and metabolism. We also review some of the human studies addressing circadian disruption and cancer incidence as well as some controlled laboratory studies connecting the two in pre-clinical models. Finally, we discuss the tremendous opportunity to use circadian approaches for future prevention and treatment in the context of cancer in specific organs.