Circadian rhythms and new options for novel anticancer therapies

Abstract

Circadian rhythms and new options for novel anticancer therapies Ursula Prosenc ZmrzljakFaculty of Medicine, Center for Functional Genomics and Bio-Chips, Institute of Biochemistry, University of Ljubljana, Ljubljana, SloveniaAbstract: The patterns of activity/sleep, eating/fasting, etc show that our lives are under the control of an internal clock. Cancer is a systemic disease that affects sleep, feeding, and metabolism. All these processes are regulated by the circadian clock on the one hand, but on the other hand, they can serve as signals to tighten up the patient's circadian clock by robust daily routine. Usually, anticancer treatments take place in hospitals, where the patient's daily rest/activity pattern is changed. However, it has been shown that oncology patients with a disturbed circadian clock have poorer survival outcomes. The administration of different anticancer therapies can disturb the circadian cycle, but many cases show that circadian rhythms in tumors are deregulated per se. This fact can be used to plan anticancer therapies in such a manner that they will be most effective in antitumor action, but least toxic for the surrounding healthy tissue. Metabolic processes are highly regulated to prevent waste of energy and to ensure sufficient detoxification; as a consequence, xenobiotic metabolism is under tight circadian control. This gives the rationale for planning the administration of anticancer therapies in a chronomodulated manner. We review some of the potentially useful clinical praxes of anticancer therapies and discuss different possible approaches to be used in drug development and design in the future.Keywords: circadian rhythms, cancer, chronotherapy, detoxification metabolism