With about 19.3 million new cancer cases and 10 million cancer deaths reported globally in 2020, cancer has become a serious public health concern worldwide.1 Despite the availability of several treatment options such as chemotherapy, radiation, and surgery, doctors are never able to reassure their patients that their cancer has been completely cured. The risk of metastasis and recurrence always looms on the horizon. Why is this the case?2
Cancer cells can spread to various parts of the body from the main tumor. These cells may hide in other organs such as bones to evade the effects of chemotherapy and radiation. Or their numbers are lowered by therapy to the point that diagnostic tests cannot identify them. Hence, when these cells become active, they form secondary tumors, which are notoriously difficult to treat. These sleeping cells are the fundamental cause of cancer therapy failure and the deaths of millions of people. These cells, however, may awaken in some patients while staying dormant in others for the rest of their lives. Why does this happen? This question has long baffled researchers all aroundthe world.2
Researchers have recently made significant progress in understanding the behavior of these slumbering cancer cells, where they might hide, and why they may awaken. It has been revealed in a study of ER-positive breast cancer cells, published in Nature Medicine, that mitotic genes are unregulated during the resting phase, leading to higher metastatic proficiency.3
According to this study, cancer cells spread faster through the bloodstream when a person is asleep. Isn’t it shocking? Should we discuss it? The following section will explore the study findings in detail.
Previously, it was assumed that because cancer cells are mutated, sleep patterns and hormone levels would have little effect on their spread. However, a study published in 2014 showed that disrupting circadian rhythms with disturbed sleep-wake cycles may increase the risk of breast cancer and other disorders by reducing the nocturnal production of melatonin, a hormone that inhibits breast cancer growth. 4
Moreover, researchers recently observed that over 90% of CTCs in mice were detected in blood samples taken while they were resting. To confirm these findings, the researchers obtained blood samples from 30 women hospitalized for breast cancer at 4 a.m. and 10 a.m.
The findings astounded the entire research team. They discovered that more than 80% of the CTCs were found in blood samples collected at 4:00 a.m., when the patients were normally asleep.5,7
The researchers tried to find the answer to this question by examining the ability of rest-and activephase CTCs to metastasize and form tumors in mouse models at different phases of the animals’ circadian cycle. When the researchers injected active and resting CTC samples into healthy mice, the mice that were injected with sleep-shed CTCs developed more tumor cells in their lungs. Moreover, when the mice were injected with key circadian rhythm hormones such as melatonin, testosterone, and glucocorticoids, the dynamics of CTC generation in their blood samples changed. In fact, insulin directly promoted the growth of tumor cells in a time-dependent manner. But, how can these findings contribute to cancer research?3-5
The greater malignancy of sleep-shed CTCs may be influenced by a number of factors that are still being explored. Melatonin and testosterone, which help control circadian rhythms, may have a role in tumor metastasis.
Furthermore, since the generation of CTCs with a high tendency to metastasize happens mostly when a person is resting, the timing of blood sampling might affect the accuracy of the test results. Hence, a new rationale for time-controlled investigation and treatment of metastasis-prone tumors is necessary to optimize cancer patients’ survival and quality of life.5
While the study’s findings are significant, researchers cautions against seeing sleep as an enemy for breast cancer patients. According to several research studies, people with cancer who sleep for less than seven hours every night are more likely to die early. Moreover, research studies have shown that interfering with animals’ circadian rhythms causes cancer to spread faster.6
The study findings do not mean that cancer patients do not require sleep or that they should sleep less. It just implies that CTCs prefer to enter the circulation at a given time during the day’s 24- hour cycle.5
In conclusion, each new study contributes to the understanding of the disease process. However, more research is required to understand the relationship between sleep patterns, hormones, and cancer. A thorough understanding of cancer etiology and metastasis may help in the development of better cancer treatment options in the future. The entire world is waiting for the cancer mystery to be resolved.4-6
1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021;71(3):209-49. DOI: 10.3322/caac.21660
2. Cancer Treatment Centers of America. Why do sleeping cancer cells awaken? cancercenter.com. Published July 20, 2021. Accessed on July 5, 2022. https://www.cancercenter.com/community/blog/2021/07/dormant-cancer-cells#
3. Morgan PJ. Cancer cells spread during sleep. frontlinegenomics.com. Published June 27, 2022. Accessed July 5, 2022. https://frontlinegenomics.com/cancer-cells-spread-duringsleep/
4. Dauchy RT, Xiang S, Mao L, et al. Circadian and melatonin disruption by exposure to light at night drives intrinsic resistance to tamoxifen therapy in breast cancer. Cancer Res. 2014;74(15):4099-110. DOI: 10.1158/0008-5472.CAN-13-3156
5. Diamantopoulou Z, Castro-Giner F, Schwab FD, et al. The metastatic spread of breast cancer accelerates during sleep. Nature. 2022;22:1-7. DOI: 10.1038/d41586-022-01724-w
6. Cappuccio FP, D’Elia L, Strazzullo P, Miller MA. Sleep duration and all-cause mortality: a systematic review and meta-analysis of prospective studies. Sleep. 2010;33(5):585-92. DOI: 10.1093/sleep/33.5.585
7. ETH Zurich. Breast cancer spreads at night, study shows: Surprising findings from cancer research. ScienceDaily. Published June 22, 2022. Accessed July 5, 2022. www.sciencedaily.com/releases/2022/06/220622113209.htm
Reviewer: Priyanka
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