Do Cancer Cells Sleep at Night?

The circadian rhythm influences bodily functions in health and disease. The study of biological cycles driven by environmental and genetic factors is an emerging field and some circadian aspects of metabolism have received considerable attention by the public (looking at you, intermitted fasting).  In cancer biology the role of the circadian rhythm is not generally considered, however an excellent review “Do malignant cells sleep at night?” provides a conceptual premise and discusses evidence in experimental models. On the question of cancer metastasis, which is at least in part dependent on the presence of circulating tumor cells (CTC) a study recently published in Nature found a striking and unexpected pattern of CTC generation dynamics in both patients with breast cancer and mouse models, highlighting that most spontaneous CTC intravasation events occur during sleep. Not only are CTC more numerous during sleep, CTC also show a marked upregulation of mitotic genes exclusively during the rest phase in both patients and mouse models, presumably enabling metastasis proficiency. In the mouse models key circadian rhythm hormones such as melatonin, testosterone and glucocorticoids dictate CTC generation dynamics, and insulin directly promotes tumor cell proliferation in vivo in a time-dependent manner. Demonstrating that cancer cells can exploit their host biological rhythms is an important first step and this knowledge will have to be integrated in the design of preventive or curative strategies.