Circadian rhythm and cell population growth

TL;DR

This paper reviews mathematical models of circadian rhythms' influence on cell proliferation, highlighting how rhythm disruptions may indirectly promote tumor growth by weakening healthy tissue defenses.

Contribution

It provides a general convexity result supporting cancer chronotherapeutics and hypothesizes an indirect effect of circadian disruption on tumor growth.

Findings

Mathematical models compare periodic control effects on cell cycles.

A convexity result supports chronotherapeutic strategies.

Disruption of rhythms may weaken healthy tissue defenses.

Abstract

Molecular circadian clocks, that are found in all nucleated cells of mammals, are known to dictate rhythms of approximately 24 hours (circa diem) to many physiological processes. This includes metabolism (e.g., temperature, hormonal blood levels) and cell proliferation. It has been observed in tumor-bearing laboratory rodents that a severe disruption of these physiological rhythms results in accelerated tumor growth. The question of accurately representing the control exerted by circadian clocks on healthy and tumour tissue proliferation to explain this phenomenon has given rise to mathematical developments, which we review. The main goal of these previous works was to examine the influence of a periodic control on the cell division cycle in physiologically structured cell populations, comparing the effects of periodic control with no control, and of different periodic controls between them. We state here a general convexity result that may give a theoretical justification to the concept of cancer chronotherapeutics. Our result also leads us to hypothesize that the above mentioned effect of disruption of circadian rhythms on tumor growth enhancement is indirect, that, is this enhancement is likely to result from the weakening of healthy tissue that are at work fighting tumor growth.