Tumour cells appear to circulate in the blood more during the night, hinting that therapies should be targeted to maximise their impact at night
Circulating breast cancer cells seen under a microscope
USC Norris Comprehensive Cancer Center/NATIONAL CANCER INSTITUTE/SCIENCE PHOTO LIBRARY
Breast cancer cells spread to other parts of the body mostly at night while people are sleeping, and not continuously throughout the day as scientists had previously thought.
This doesn’t mean that people with cancer should try to avoid sleeping to stop it from spreading, researchers warn – previous work has suggested that disrupted sleep could worsen breast cancer prognosis. But the discovery does indicate that considering the best time of day to give cancer therapies could make them more effective, says Nicola Aceto at ETH Zurich in Switzerland.
“Most cancer treatments are not designed with the intent to target tumour cells at a specific time, but are rather given with the general thought that the tumour is there, and you try to attack it at any time,” he says. “Now we understand what happens at different times better than we did before, and that [treatment] needs to be done better.”
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Aceto and his colleagues had been running another study on metastatic breast cancer – meaning it had spread to other organs – when they detected an unexpected trend. The participants’ circulating tumour cells (CTCs), cells that spread out from invasive tumours, were proliferating mostly at night.
They decided to investigate further on 30 women with breast cancer, including nine with metastatic disease, who weren’t undergoing treatment. The scientists collected blood samples at 10am and 4am in the hours prior to their cancer surgeries.
Their analysis revealed that 78 per cent of all the CTCs were found in the night-time samples, when the women had been sleeping.
The researchers then ran similar blood tests on mice that had been transplanted with four different kinds of breast cancer. They discovered that, depending on the cancer type, between 87 and 99 per cent of the CTCs came from samples taken during the animals’ sleep periods. Furthermore, the CTCs clustered – meaning they were more likely to form a new tumour – up to 278 times more in samples from sleeping mice compared with those from awake mice.
While initially surprising, the findings actually make sense, says Aceto. The immune system is heavily modulated by the body’s sleep-wake cycle, known as the circadian rhythm. Cancer tumours, however, were generally thought not to obey that rhythm, he says.
The new findings correct that misconception, but still leave many questions unanswered. “There is a certain rhythmicity, with the highest peak during sleep,” says Aceto. “Which exact moment during sleep – and whether sleeping more or less would help this – we absolutely don’t know.”
Journal reference: Nature, DOI: 10.1038/s41586-022-04875-y
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