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Cancer is a treacherous insurgent force, invading the body and hijacking natural systems to promote its campaign of destruction.

A new study shows tumors can even seize control of circadian rhythms themselves to bolster its biological hold, as reported in the journal Nature Cell Biology.

“What a tumor is doing is taking a pathway that’s already in the cell and using it to its advantage,” said J. Alan Diehl, the senior author of the study, from the Medical University of South Carolina.

The cancer cells essentially use a diversionary tactic. In an as-yet undetermined way, cancer cells boost the activity of the body’s natural unfolded protein response, or UPR.

That UPR response means the body is busy refolding those proteins – and cannot make the routine proteins that are toxic to the cancer – and can fight off the rogue cells.

The UPR activity also happens to be linked to the circadian clock – and in particular to a single protein that is connected to survival rates in certain cancers, they add.

The activation of this pathway causes a 10-hour phase shift by triggering a microRNA called miR-211, which suppresses two proteins that are circadian regulators, Bmal1 and Clock.

The researchers used a rodent model to reverse the light-dark cycles of the animals. They found that the animals’ levels of Bmal1 stopped rising and falling regularly, as naturally occurs with a normal cycle. It was the shift in light exposure that elevated UPR activity – and thereby interrupted the circadian rhythm, they report.

The investigation plunged into the tumors of Burkitt’s lymphoma, a lymphatic cancer. There they found that Bmal1 suppression continually threw off circadian timing – thereby promoting tumor progression, they write.  

“We showed that resetting the circadian rhythms in cancer cells slows down their proliferation,” said Yiwen Bu, postdoctoral researcher who was the first author on the paper.

The findings could eventually prompt a reconsideration of how – and most importantly, when – cancer treatments are administered, they added.

“Physicians are beginning to think about timing delivery of therapies in such a way that, say, if we deliver a drug at a certain time of day, we’ll get better on-target effects on the cancer and less toxicity in the normal cells,” said Diehl.

Dr. Yiwen Bu and Dr. J. Alan Diehl are hoping their research will lead to a way to restore a cancer cell’s biological clock and give cancer patients a better chance at survival. Photo: MUSC
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