Marker rhythms for cancer chronotherapy. From laboratory animals to human beings.

The author reviews basic knowledge related to circadian rhythmicities potentially harmful for cancer chronotherapy scheduling in laboratory rodents and in human beings. Circadian rhythms have been evidenced both in animals and in humans, in metabolically active or actively dividing healthy tissues, as well as in most experimental tumors and in some human cancers. These phenomena, taken together with the chronopharmacology of anticancer drugs, can account for the diurnal variability of tolerance and of antitumor activity of oncolytic drugs. Of interest in clinical practice, recently large clinical trials have confirmed the achievement of an improvement in clinical outcome from overall delivered higher doses of chemotherapy allowed by the chronotolerance concept. The possibility of proposing individualized chronotherapy schedules from precise gauging (even in saliva or in urine) of cortisol and various human tumor markers is also discussed.