The spread of cancer cells throughout the body, known as metastasis, is responsible for up to 90 per cent of deaths in patients with cancer. But not all metastases are created equal: recent scientific research shows that cancer can be more aggressive at night, sending out more cells through the blood to set up shop in new places in the body.
During metastasis, tumours located in one part of the body can send small expeditions of cancerous cells, known as circulating tumour cells (CTCs), to travel through the blood and start new tumours in distant organs. Scientists expected that tumours would constantly shed CTCs into the blood, or at least that they wouldn´t be particular about the time of the day to do the shedding. But the new studies in both mice and breast-cancer patients have shown that these cells are travelling through the blood mostly during resting time. And to add insult to injury, these night-time CTCs appear to be more aggressive and better prepared to establish brand new tumours. The study was carried out by scientists in the Swiss Federal Institute of Technology (ETH) Zurich, and the University of Basel, in Switzerland.
“The findings that cancer cells may be more likely to spread in the blood of people affected by breast cancer to other parts of the body during sleep is an exciting discovery, as it could indicate that the time of day for blood sample collection or for administering cancer treatments may be an important consideration,” says Dr Claire Kilty, the Irish Cancer Society’s acting head of research. “The results of this paper do not mean, however, that people affected by breast cancer should avoid sleep or alter their sleep patterns, as this may be detrimental to their overall health.
“Instead, the results provide a new avenue of research to pursue to improve the treatment and wellbeing of people with breast cancer. We welcome further research on this topic to determine if the timings of current cancer therapies need to be optimised to improve patient outcome.”
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Dr Annie Curtis, senior lecturer at the school of pharmacy and biomolecular science at RCSI – University of Medicine and Health Sciences, agrees. “I think it is important to be clear that the message from this study is not that sleep accelerates metastatic spread. Many studies have found that insufficient sleep is known to promote cancer. Instead, it seems that cancer has co-opted the biological processes which occur during the sleep state for its own advantage. This study also shows the importance of when we do diagnostic tests and also when we treat for cancer.”
Our bodies carry a biological clock that tells our cells when to do certain tasks. Small molecules like hormones are only produced at certain times of the day, and can control our hunger, ability to concentrate and ultimately result in being alert during light hours and sleepy when it´s dark. Studies have found that the risk of breast cancer may increase when the biological clock is altered, such as in people working night shifts or odd hours. However, until now it was believed that cancer cells would not be on the clock like our normal cells are.
The study looked for CTCs in blood samples from 30 women receiving treatment for breast cancer. The samples were taken at 4am and 10am, and the researchers unexpectedly found that almost 80 per cent of the CTCs were found in the earlier sample, taken while the patients were resting.
To confirm these results, scientists carried out further research in mice. These experiments had to take into account that a mouse´s biological clock runs opposite to ours, with night-time being the period of activity and bright hours used for resting. Just as they had found in patients, CTCs were more abundant in the blood of mice carrying tumours during resting time.
In a further step, scientists took CTCs from the blood during resting and active periods, labelled them with different colours and implanted them together into healthy mice. They found that CTCs that had been circulating during resting time (distinguished by their colour) were more capable of starting new tumours than those isolated from the blood of mice during active times. These results suggested that not only are there more CTCs going around the blood during resting periods, but also that these cells are more aggressive and better able to spread and metastasise.
Dr Curtis thinks this study is “hugely significant”. “It adds to [a] growing body of evidence that many biological processes, both in healthy and disease states, have a 24-hour rhythm. What I found remarkable is that it is not just the number of circulating tumour cells that are increased during the rest phase, but also each cell’s capacity to develop into a tumour is increased during the rest phase. It is interesting that other studies have shown that immune cells also migrate around the body more during the rest phase.”
“These results provide more evidence that for certain types of treatment including cancer, an optimal time of day to treat might exist. Other studies have clearly shown that this timing approach, also called ‘chronotherapy’, can increase how well we tolerate a drug as well as its efficacy,” Dr Curtis added.
However, things are always more complicated than they seem. “Basically metastatic potential is a multifaceted event and CTCs are part of that, but not the full story,” says Dr Alex Eustace, assistant professor in biotechnology at Dublin City University. More research is needed to find out how this work can benefit patients with cancer.