An integrative mathematical model for timing treatment toxicity and Zeitgeber impact in colorectal cancer cells

Abstract

Increasing evidence points to a role of the circadian clock in the regulation of cancer hallmarks with a strong impact on the understanding and treatment of this disease. Anti-cancer treatment can be personalized considering treatment timing. Here we present a new mathematical model based on data from three colorectal cancer cell lines and core-clock knock-outs, which couples the circadian and drug metabolism network, and that allows to determine toxicity profiles for a given drug and cell type. Moreover, this model integrates external Zeitgebers and thus may be used to fine-tune toxicity by using external factors, such as light, and therefore, to a certain extent, help fitting the endogenous rhythms of the patients to a defined clinic routine facilitating the implementation of time-dependent treatment in clinical practice.