The Nightlife of Cancer Metastases

Nightlife of Cancer Metastasis

UPDATE ; DAY

Surprising results show that the vast majority of cancer cells that will form metastases circulate in the blood during the night. This discovery could revolutionize cancer treatment by modifying the administration schedules of anti-cancer drugs to improve their effectiveness. 

Cancer is a particularly dangerous disease when cells from a tumor manage to sneak into the bloodstream and establish themselves elsewhere in the body. These new tumors, called metastases, are extremely difficult to eradicate and are still responsible for around 90% of cancer-related mortality today. 

Better understand how these circulating tumor cells can form these metastases is therefore absolutely essential to improve the effectiveness of treatments and the survival of patients with advanced cancers. 

Circulating tumor cells (CTCs) can circulate in the bloodstream as single cells or as clumps containing two or more cells. CTC clusters also frequently contain other non-cancerous cells, certain immune cells for example, and it seems that the formation of these aggregates favors the progression of metastases. 

On the other hand, the factors that govern the release of these CTCs, as well as their aggressiveness in forming metastases, remains poorly understood.

Nocturnal release

According to a study recently published in the prestigious Nature, one of the key factors in the aggressiveness of metastases is the time of day when tumor cells are released into the bloodstream(1). &nbsp ;

In this study, Swiss researchers analyzed blood samples from 30 women with breast cancer, taking the samples at 4 a.m. (rest period) and 10 a.m. morning (active period).  

To their surprise, they found that 80% of all circulating tumor cells in the blood were present in samples taken during the resting phase, in the middle of the night.

Not only CTCs were in greater numbers overnight, but these cells also exhibited greater capacity for growth and were more likely to form metastases when injected into animal models. 

Molecular analysis using state-of-the-art biochemical tools (single-cell RNA sequencing) revealed that the greater aggressiveness of nocturnal circulating cells was due to a marked increase in the levels of genes involved in cell division compared to circulating cells present in samples collected during the day. Like several other physiological processes (metabolism, secretion of hormones such as cortisol and melatonin), it therefore seems that the process of metastasis is governed by a circadian rhythm, with a peak in activity that occurs during the night.

Sleep is important in fighting cancer

The discovery that cells forming metastases are more active at night obviously does not mean that women with breast cancer should deprive themselves of sleep. On the contrary, it is important to sleep well, as several studies have clearly shown that people with cancer who generally sleep less than seven hours a night are at higher risk of death. 

It is especially with regard to the treatment of cancer that the discovery of a circadian rhythm governing the process of metastasis can have enormous positive repercussions.  

Since the degree of aggressiveness of circulating cancer cells varies over time, it is thought that the timing of an anti-cancer drug will have a significant impact on its effectiveness.  

Thus, given that the peak of Metastatic activity appears to be highest during the night, treatment performed during this time window could increase the chances of destroying tumor cells when they pose the greatest danger to the body. 

< p>♦ (1) Diamantopoulou Z and co ll. The metastatic spread of breast cancer accelerates during sleep. Nature, published June 22, 2022.