Women who work night shifts have substantially higher risks of breast, digestive system, and skin cancers, a recent study found. The findings reinforced a connection researchers have observed between cancer and the circadian clock, a biological system that controls the daily schedule of physiological processes.
Now, in findings that could lead to a new class of cancer drugs, researchers have uncovered details about a key molecular link between circadian rhythm and cancer.
The nuclear hormone receptors REV-ERBα and REV-ERBβ are essential components of the body’s circadian clock. Gabriele Sulli and Satchidananda Panda at Salk Institute for Biological Studies and coworkers show that when each of two small organic molecules, SR9009 and SR9011, turn on the receptors in cell culture, the interactions kill breast, colon, leukemia, melanoma, and brain cancer cells, as well as dormant premalignant cancer cells (Nature 2018, DOI: 10.1038/nature25170).
The data suggest that circadian clock-targeted agents could treat a wide range of cancers with few side effects, the researchers say. But they point out that further safety testing and trials in people are necessary. The Salk team found that the two compounds kill cancer cells by inhibiting lipid production and “autophagy,” a process in which cells degrade unwanted cellular components. Cancer cells need both metabolic processes to grow and reproduce.
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