Chronotherapeutics: the relevance of timing in XXXX therapy.

@entity1 @entity901 @entity4181 @entity5 @entity14 @entity1487
BACKGROUND: Cell physiology is regulated along the 24-h time scale by a circadian timing system composed of molecular clocks within each cell and a central coordination system in the brain. The @entity1 molecular clock is made of interconnected molecular loops involving at least 12 circadian genes. The cellular clocks are coordinated by the suprachiasmatic nuclei, a hypothalamic pacemaker which also helps the organism adjust to environmental cycles. The rest-activity rhythm is a reliable marker of the circadian system function in both rodents and @entity1 . This circadian organization is responsible for predictable changes in the tolerability and efficacy of anticancer agents, and possibly also in @entity5 promotion or growth. METHODS: Expected least toxic times of chemotherapy were extrapolated from experimental models to @entity1 subjects with reference to the rest-activity cycle. The clinical relevance of the chronotherapy principle, i.e. treatment administration as a function of rhythms, has been demonstrated in randomized multicenter trials. RESULTS: Chronotherapeutic schedules have been used to safely document the activity of the association of @entity901 , @entity1487 and @entity4181 against metastatic @entity14 and to set up a new medicosurgical management of this disease which achieved unprecedented long term survival. CONCLUSION: The chronotherapy concept offers further promises for improving current @entity5 as well as for optimizing the development of new anticancer or supportive agents.
