What, how and (especially) when: chronoparmacological approach in cancer therapies.

TREBUCQ, LAURA LUCÍA; MARPEGAN, LUCIANO; GOLOMBEK, DIEGO A.; CHIESA, JUAN J.

Sleep Science

Brazilian Association for Sleep Science

Año: 2020

1984-0659

Most physiological and behavioural processes in mammals show 24-h period oscillations regulated by an endogenous circadian clock. Drugs pharmacokinetics and pharmacodynamics are not the exception. Determining the time of day when the therapeutic effect of a certain drug is maximum and, in turn, its side effects are minimum, is the main objective of chronopharmacology. The daily oscillations in processes necessary for the absorption, metabolization, distribution and excretion of drugs determine the chronopharmacokinetics, while the oscillations of the targets, receptors, enzymes and signaling systems of these drugs determine the chronopharmacodynamics. Two concepts are important when analyzing the therapeutic value of a drug: toxicity and effectiveness. Indeed, studying the dependence of drug effect on the circadian time of administration may help to determine the putative daily variation in their therapeutic index. Many anti-tumor compounds have circadian variations in their pharmacokinetics and dynamics, depending on the time of administration. Nevertheless, not many of them are currently administered according to a chronopharmacological approach. Studying the time- dependent effect of oncological drugs is essential to generate therapeutic advances in cancer treatment.