Time for chronotherapy? Clock genes dictate sensitivity to cyclophosphamide
Sensitivity to chemotherapeutic agents depends on the specific molecular state of the circadian clock.
Temporal organization of biological processes is a critical feature of life. In addition to orderly, carefully timed developmental processes, precise temporal organization is also observed on a daily time scale. On Earth, organisms ranging from bacteria to humans have evolved internal timekeeping mechanisms called circadian clocks that control biochemistry, physiology, and behavior to coordinate with the 24-hour day (1–3). Circadian clocks have long been known to drive rhythms in such things as activity, sleep, and hormone secretion, but in recent years it has become clear that these clocks influence the normal homeostasis of organisms on a profound scale, controlling processes as diverse as cell cycle regulation, cell signaling, metabolic events, and cognitive function. Disruption of clock function in mammals results in abnormalities in many physiological functions, resulting in increases in risks for cardiovascular and gastrointestinal diseases, sleep abnormalities, and cancer (reviewed in refs. 1 and 4). In a recent issue of PNAS, Gorbacheva et al. (5) describe a mechanistic link between the circadian clock and sensitivity to the chemotherapeutic agent cyclophosphamide (CY).
Temporal organization of biological processes is a critical feature of life. In addition to orderly, carefully timed developmental processes, precise temporal organization is also observed on a daily time scale. On Earth, organisms ranging from bacteria to humans have evolved internal timekeeping mechanisms called circadian clocks that control biochemistry, physiology, and behavior to coordinate with the 24-hour day (1–3). Circadian clocks have long been known to drive rhythms in such things as activity, sleep, and hormone secretion, but in recent years it has become clear that these clocks influence the normal homeostasis of organisms on a profound scale, controlling processes as diverse as cell cycle regulation, cell signaling, metabolic events, and cognitive function. Disruption of clock function in mammals results in abnormalities in many physiological functions, resulting in increases in risks for cardiovascular and gastrointestinal diseases, sleep abnormalities, and cancer (reviewed in refs. 1 and 4). In a recent issue of PNAS, Gorbacheva et al. (5) describe a mechanistic link between the circadian clock and sensitivity to the chemotherapeutic agent cyclophosphamide (CY).
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