CIRCADIAN CONTROL OF CANCER CELL PROLIFERATION AND RESPONSE TO ANTICANCER TREATMENTS

Abstract

Circadian clocks are intrinsic, coordinated systems that operates in all cells and enable organisms toanticipate environmental changes, thereby adapting their behaviour, physiology and metabolism to theappropriate time of day, thus contributing to maintain body homeostasis. Disruption of these rhythmshas a profound influence to human health and has been linked to many diseases, from depression tometabolic disorders to cancer. Indeed, the circadian timing system controls rhythmic events in cellcycle, DNA repair and apoptosis in both normal tissue and cancer and drives daily rhythmic changesin drug metabolism. Consequently, the toxicity and anticancer activity of common anticancer drugscan be significantly modified by the time of administration in both experimental models and in cancerpatients. The molecular mechanisms at the base of this event are still poorly understood and this is oneof the factors that limit the establishment of a successful cancer chronotherapy in clinical practice. Ourresearch is focused on identifying the molecular mechanisms linking circadian rhythm to cancer cellproliferation, explore the mechanisms responsible for the beneficial effects of circadian administrationof anticancer drugs, and deciphering the direct effect of specific clock components on different cellularfunctions in response to anticancer treatment.