Circadian Rhythms and Cancer: What’s the Connection?

Circadian rhythms describe the roughly 24-hour cycle that many of our life-sustaining processes operate on. In humans, as in all animals, circadian rhythms regulate hundreds of activities, from sleep patterns to body temperature to digestion.

Life in industrialized societies can play havoc with natural circadian cycles, which are most strongly influenced by changes in light that occur over the course of the day. The body’s natural response to fading daylight, for example, can be disturbed by a lifestyle that involves considerable light exposure well into the night. Chronic disruptions to natural circadian rhythms have been linked to an increase in a variety of disorders, including cancer. Studies have shown that cancer development is closely related to a loss of circadian balance in how we burn energy, respond to infection and disease, and age.

Circadian rhythms are continually at work within individual cells, controlling how they grow, divide, metabolize nutrients, repair damage to their DNA, and a perform an array of other functions. Abnormalities in these areas are among the major characteristics of cancer, and there’s mounting evidence that long-term disruptions of circadian rhythms can increase the risk of developing cancer in some individuals. As a result, scientists have begun to explore how we can potentially harness the circadian machinery of cells to improve the treatment of cancer.

Circadian rhythms describe the roughly 24-hour cycle that many of our life-sustaining processes operate on.
Circadian rhythms describe the roughly 24-hour cycle that many of our life-sustaining processes operate on.

One recent study shows the promise of that approach. In laboratory experiments, scientists showed that compounds that target two protein components of the circadian clock can kill several types of cancer cells without harming normal cells. A second series of experiments showed that the compounds also killed a type of senescent cells, which are precancerous cells that have stopped growing due to a cancer-causing mutation.

The study “highlights how circadian rhythms and cancer biology intersect, how important these two field are to each other, and how we might begin to explore that relationship to target cancers,” said Joanna Watson, PhD, a program director in the Division of Cancer Biology at the National Cancer Institute, who was not involved in the study.

A recent study in melanoma found that when the circadian rhythm in tumor cells was impaired because of low activity in certain genes, treatment with drugs able to improve that rhythm produced a slowdown in tumor growth.

Scientists are currently developing drugs that activate or interfere with other components of the circadian clock. These drugs, in combination with each other or with other types of agents, may have powerful anti-cancer effects, but much work needs to be done before that is known, researchers say.

Circadian rhythms influence not only the inner workings of cells but also the effectiveness of drug agents. Because circadian rhythms are often disrupted in cancer patients, it can be important to tailor treatment to each patient’s unique rhythms, researchers believe. One approach is to adjust cancer drug delivery using programmable pumps or formulations that release the drug at specific times. Such techniques may make the drugs easier to tolerate and may in some cases prolong survival, researchers found.

In many cases, the potential benefits of administering drugs at a particular time of day are still unclear. For example, a 1997 study found that children with acute lymphoblastic leukemia who took the oral drugs methotrexate and 6-mercaptopurine in the evening survived longer without complications or advance of the disease than did those who took them in the morning. However, a follow-up study in 2014 found no advantage of taking the drugs in the evening.

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