Treatments Just in Time

Most medical procedures are scheduled around the doctor's availability rather than the patient's biological clock. That may soon change, based on new findings that suggest the molecular clock directs cell division. Coordinating cancer therapies to accommodate the body clock could lead to faster healing after surgery, more effective targeting of the tumor cells, and fewer side effects.

Many aspects of our physiology, such as blood pressure and body temperature, cycle on a 24-hour rhythm called the circadian clock. This system keeps the body in sync with Earth's light-dark cycle and relies on several interacting genes. Last year, researchers reported that mice with a mutation in one of these clock genes develop cancer more readily than normal mice, suggesting that the clock could influence cell division. They found that the clock gene controls the cyclical expression of several proteins important for cell division.

To further examine the relationship between the circadian clock and cell division rhythms, molecular neurobiologist Hitoshi Okamura of Kobe University, Japan, and his colleagues looked at cell division following liver surgery in mice. Removing part of the liver stimulates cell proliferation as the organ regrows, making it easy for researchers to locate and examine actively dividing cells. They found that cell division started at the same time of day, regardless of when the surgery was done: In mice operated on at dawn, most cells divided at dawn 2 days later, but if surgery took place 8 hours after first light, cell division still peaked at dawn on the second day. Probing deeper, the scientists found three genes involved in cell division, whose activity reflected the circadian time. These genes appeared to direct the cells to begin dividing. In mice engineered to lack timekeeping genes, cells didn't do that and regrowth of the liver slowed significantly.

Molecular geneticist Cheng Chi Lee of Baylor College of Medicine in Houston, Texas, says the study bolsters previous work and provides "a wonderful demonstration of the molecular mechanism relating the clock to cell division cycle." Using the activity of these cell cycle genes as an indicator of the body's clock time, Lee says, physicians might one day schedule surgery when cells are dividing to maximize regeneration of tissue for healing, or deliver chemotherapy when normal cells are resting, thereby stepping up the attack on cancer cells and minimizing side effects.

Related sites
Background on circadian rhythms
Cheng Chi Lee's home page
International consortium researching chronobiology and cancer

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