Coupling between the cell cycle and the circadian clock: Lessons from computational modelling and consequences for cancer chronotherapy

Chronotherapy aims at optimising the time of day and dosing of drugs administration. This is a promising perspective because the toxicity and efficacy of many drugs show a dependence on the time of the day at which they are administrated. Efficient cancer chronotherapy requires a good understanding of the interplay between the cell cycle and the circadian clock. Computational models offer a way to study the dynamics resulting from the coupling between these two biological oscillators and to predict successful therapeutic protocols. We review here recent advances and highlight key challenges for further developments of predictive mathematical models.