Beating the clock: targeting circadian rhythms to reduce chemotherapy-associated toxicity

Chemotherapy-associated toxicity represents a significant clinical challenge for the treatment of cancer, limiting the dose of anti-cancer agents that a patient is able to receive. Current drug development protocols tend to imply that the pharmacokinetics and pharmacodynamics of a drug are comparable no matter what time of day, time of year, or day of menstrual cycle the drug is administered on. However, it is increasingly recognised that the circadian rhythm system, responsible for co-ordinating both the physiological and cellular functions of an organism over a 24-hour period, plays an essential role in modulating cell cycle and drug metabolism. By taking advantage of the naturally occurring differences in circadian rhythms between cancer cells and healthy cells, it is possible to significantly increase the tolerability and efficacy of chemotherapeutic agents. While much remains to be done to elucidate the molecular mechanisms of circadian rhythms, there is promising evidence to suggest that exploiting these differences may allow clinicians to further personalise cancer treatment, and to reduce the significant toxicity and side-effect profile of chemotherapeutic agents.