Clocks, cancer, and chronochemotherapy.

1. Science. 2021 Jan 1;371(6524):eabb0738. doi: 10.1126/science.abb0738. Clocks, cancer, and chronochemotherapy. Sancar A(1), Van Gelder RN(2). Author information: (1)Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. aziz_sancar@med.unc.edu russvg@uw.edu. (2)Departments of Ophthalmology, Biological Structure, and Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA 98104, USA. aziz_sancar@med.unc.edu russvg@uw.edu. The circadian clock coordinates daily rhythmicity of biochemical, physiologic, and behavioral functions in humans. Gene expression, cell division, and DNA repair are modulated by the clock, which gives rise to the hypothesis that clock dysfunction may predispose individuals to cancer. Although the results of many epidemiologic and animal studies are consistent with there being a role for the clock in the genesis and progression of tumors, available data are insufficient to conclude that clock disruption is generally carcinogenic. Similarly, studies have suggested a circadian time-dependent efficacy of chemotherapy, but clinical trials of chronochemotherapy have not demonstrated improved outcomes compared with conventional regimens. Future hypothesis-driven and discovery-oriented research should focus on specific interactions between clock components and carcinogenic mechanisms to realize the full clinical potential of the relationship between clocks and cancer. Copyright © 2021, American Association for the Advancement of Science. DOI: 10.1126/science.abb0738 PMID: 33384351 [Indexed for MEDLINE]