Circadian cancer chronotherapy

The present modeling approach to circadian cancer chronotherapy is based on an automaton model for the cell cycle. Continuous approaches to cell cycle progression have also been used to study the link between cell proliferation and circadian rhythms [44] and to determine, in conjunction with optimal control theory, the most efficient circadian schedules of anticancer drug administration [45]. Including more molecular details of the cell cycle in continuous models for cell populations represents a promising line for future research. Hybrid models incorporating molecular details into the automaton approach presented here will also likely be developed. 

Here, as in a previous publication [33], we used the cell cycle automaton model to probe the cytotoxic effect of various patterns of circadian or continuous 5-FU delivery. The results provide a framework to account for experimental and clinical observations, and to help us predict optimal modes of drug delivery in cancer chronotherapy. By explaining the differential cytotoxicity of various circadian schedules of 5-FU delivery, the model clarifies the foundations of cancer chronothera-peutics. In view of its versatility and reduced number of parameters, the automaton model could readily be applied to probe the administration schedules of other types of anticancer medications active on other phases of the cell cycle. 

Levi F (2001) Circadian chronotherapy for human cancers. Lancet Oncol 2 307-315... 

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