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Scientists at University of North Carolina at Chapel Hill (UNC) have made a breakthrough discovery in the field of cancer research. A new paper, published this week in Proceedings of the National Academy of Sciences, explains that tinkering with a cancer cell’s circadian rhythm makes it more susceptible to chemotherapy and thus easier to eradicate.
A circadian rhythm is how a body maintains the 24 hour cycle of sleep and wakefulness—it is literally our biological clock. Past studies have shown that intentionally disturbing a human’s circadian rhythm can lead to severe health problems. In one of the largest experimental observations, “the Nurses' Health Study found that nurses who worked the night shift had a higher incidence of breast cancer than those who worked days. Another study of flight attendants whose internal biological clocks had been wrecked by travel on transatlantic flights produced similar findings.” [EurekAlert]
Individual cells have their own personal biological clock, one that feeds into the overall circadian rhythm of the entire body. Because biological clocks were so closely related to cancer, scientists at UNC began to study what effect altering a cancer cell’s individual clock would have on tumor growth. By deleting one of the four essential “clock genes” (the genes responsible for the control of circadian rhythms), researchers found something quite unexpected. Instead of increasing the rate of tumor genesis (or growth of tumors) in normal mice, the rate of cancer actually slowed down.
Surprised by that find, researchers decided to go a step further. The same clock gene, cryptochrome, was deleted in mice that have mutations in p53, a gene that is often defective in human cancers. These mice are predisposed to develop cancer. Once again, the findings were contrary to what was expected: “The researchers found that disturbing the internal clock in these mice did not speed up the onset of cancer, but instead had the opposite effect – it extended their lives by 50 percent.” [EurekAlert]
Closer investigation showed that by mutating cryptochrome, cancer cells were being eliminated via the activation of intracellular signals that help destroy dangerous cells. Author of the paper Aziz Sancar, M.D., Ph.D., a member of the UNC Lineberger Comprehensive Cancer Center and Sarah Graham Kenan Professor of Biochemistry and Biophysics in the UNC School of Medicine, stated that the mutation “tactic essentially makes cancer cells more likely to commit cell suicide – through a process known as apoptosis – in response to the stresses of UV radiation or chemotherapy.”
This is great news for those suffering from cancer, especially cancer types are defective in the p53 gene (which is over 50% of human cancers). Not only does this mutation slow the progression of cancer, but therapeutic application of the findings may one day improve the successfulness of chemotherapy.
And speaking of chemotherapy, the Sancar lab has also shown that “chemotherapy treatment for cancer is most effective at certain times of day because that is when a particular enzyme system – one that can reverse the actions of chemotherapeutic drugs – is at its lowest levels in the body.” [EurekAlert] By combining both of these circadian rhythm findings, the Sancar lab may be well on its way to establishing the most effective treatment of cancer yet.
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