Tumor cells appear to circulate more in the blood at night, implying that therapies should be tailored to maximize their impact at night.
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Breast cancer cells spread to other parts of the body primarily at night while people sleep, rather than continuously throughout the day, as scientists previously believed.
Researchers caution that this does not mean people with cancer should try to avoid sleeping to prevent it from spreading – previous research has suggested that disrupted sleep may worsen breast cancer prognosis. However, the discovery suggests that considering the best time of day to administer cancer therapies could make them more effective, according to Nicola Aceto of ETH Zurich in Switzerland.
"Most cancer treatments are not designed with the intent of targeting tumor cells at a specific time," he says. "Rather, they are given with the general thought that the tumor is there, and you try to attack it at any time." "We now have a better understanding of what happens at different times than we did before, and that [treatment] needs to be done better."
Aceto and his colleagues were conducting another study on metastatic breast cancer, which had spread to other organs when they noticed an unexpected trend. CTCs, which are cells that spread out from invasive tumors, proliferated mostly at night in the participants.
They decided to look into 30 women with breast cancer who were not receiving treatment, including nine with metastatic disease. In the hours before their cancer surgeries, the scientists took blood samples at 10 a.m. and 4 a.m.
Their analysis revealed that 78% of all CTCs were found in the women's nighttime samples when they were sleeping.
The researchers then performed similar blood tests on mice implanted with four different types of breast cancer. They discovered that, depending on the cancer type, samples taken during the animals' sleep periods contained between 87 and 99 percent of the CTCs. Furthermore, CTCs clustered – meaning they were more likely to form a new tumor – up to 278 times more in sleeping mice samples than in awake mice samples.
According to Aceto, while the findings were initially surprising, they now make sense. The body's sleep-wake cycle, known as the circadian rhythm, has a strong influence on the immune system. Cancer tumors, on the other hand, were thought to defy that rhythm, he claims.
The new findings correct that misconception, but many questions remain unanswered. "There is a rhythmicity," Aceto says, "with the highest peak during sleep." "We absolutely don't know which exact moment during sleep – and whether sleeping more or less would help this."
Reference: DOI: 10.1038/s41586-022-04875-y