Chronic disruptions of circadian rhythms, or internal body clocks, have been linked to an increased risk of cancer. Yet the underlying mechanisms by which these disturbances promote tumor growth have remained mysterious. In a new study in the journal PLOS Biology, researchers from the Perelman School of Medicine show that circadian disruptions trigger an increase in cell proliferation that, ultimately, shifts the cell-cycle balance and stimulates the growth of tumors in mice.
The investigation also revealed that the timing of cancer treatment in mice can have an impact on its effectiveness. One drug used for breast cancer treatment, Palbociclib, was found to be more effective when given in the morning than at night. This could enable a lower dose of the drug to be used, potentially reducing side effects.
However, the researchers found that chronic circadian disruption—achieved by simulating frequent jet-lag—reduced the efficacy of the therapy in human cultured cells, a finding that was validated in mice.
“We suggest that chronic disruption of the normal circadian rhythm tips the balance between tumor-suppressive and tumor-progressive gene expression to favor tumor growth,” says senior author Amita Sehgal, a professor of neuroscience and director of Penn’s Chronobiology Program. “Better understanding of the molecular effects of jet lag, shift work, and other sources of chronic disruption may lead to strategies to minimize the increased cancer risk associated with these behaviors, as well as to better treatment strategies, including timing delivery of cancer therapy for maximum benefit.”
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