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Longevity Briefs: Why Cancer Drug Effectiveness Could Depend On The Time Of Day

Posted on 13 December 2021

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Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: The circadian clock is a biological timing system that cycles roughly every 24 hours, even in the absence of environmental cues like light and dark. The circadian clock affects many process within our bodies, including the timing of cell division. Because of this, mutations in genes that control the circadian clock may disrupt the control of cell division, making cancers more likely to develop. Furthermore, tumours grow in a rhythmic pattern based on the circadian clocks of the cancer cells, which can be de-synchronised with those of healthy cells. We might be able to capitalise on this fact by administering cancer treatments at a stage of this cycle when they will be most toxic to the cancer cells and least toxic to the regular cells. This approach is known as tumour chronotherapy. Unfortunately, there is still much that we don’t understand about how the circadian clock interacts with the cell division cycle, and chronotherapy has yet to enter standard practice.

circadian rhythm
A conventional circadian rhythm. These times are not universal for everyone – the clock can be shifted backwards and forwards in response to environmental cues, mainly exposure to light. That’s why you don’t stay jetlagged forever!

What did the researchers do: In this paper, researchers review our current knowledge of the circadian rhythm, the genes involved, and their interactions with cell division and cancer development.

Key takeaway(s) from this research: The authors conclude that while understanding the link between the circadian clocks of cancer cells and and their division is important, it is difficult in practice to correctly time cancer therapies to take advantage of this relationship. Some researchers have also called into question the nature of the relationship between disrupted circadian rhythms and cancer. They suggest that increased risk of cancer is not the direct result of disrupted circadian rhythm itself, but rather that the genes controlling circadian rhythm have additional functions that are important in protection against cancer.

It’s also difficult to prove beyond all doubt that disrupted circadian rhythm causes cancer (and not the other way around). It’s not ethical to disrupt the circadian clocks of random groups of people to see if they get cancer more often, so we rely on observational studies (observing a group of people without intervening in their actions), which cannot prove causation.

Despite these issues, there are many ongoing clinical trials attempting to use chronotherapy to improve cancer treatment. Shift work, jet lag and sleep disturbance are now part of many people’s lives, and are all associated with the development of cancer. If disruption of the circadian rhythm does explain this relationship (which still seems probable), then understanding how circadian clocks interact with the cell division cycle might still help with cancer prevention, even if chronotherapy proves unviable.

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