Scientists studying relationships between different types of cells have encountered some new and potentially important information about how -- and when -- cancerous tumors grow most aggressively. According to a new study, cancerous tumors may grow faster at night, during the hours typically taken up by sleep. Their discovery may point the way toward new, circadian-aligned strategies for treating cancer.
Researchers at Israel's Weizmann Institute of Science have found evidence that suggests some cancers may grow more quickly during nighttime, resting hours than during the waking day.
The finding came as a surprise to researchers, who originally set out to examine the relationships between cell receptors, molecules that are involved in cell-to-cell communications. In particular, researchers were investigating the relationship between two types of cell receptors. The first receptor, EGFR (epidermal growth factor receptor), assists in cell growth and division. EGFR is involved in normal cell growth, and also in the growth of cancer cells. High levels of EGFR are found in many cancer cells, and one type of current cancer treatment works to fight cancer by inhibiting EGFR levels.
The second receptor involves a type of steroid hormone known as glutocorticoids (GC). Glutocorticoids perform a number of essential functions, one of which is a role in supporting daytime energy and alertness. When the body is under stress, levels of glutocorticoids rise sharply, heightening and sharpening a sense of alertness. Cortisol, often referred to as the "stress hormone," is one important glutocorticoid.
Glutocorticoid hormone levels rise and fall in alignment with a 24-hour, circadian cycle. During active daytime hours, GC levels are at their highest, when we need to be alert and energized. GC levels plummet to their lowest levels at night during sleep, before rising again as morning arrives.
Scientists investigated how the circadian changes in GC hormone levels might affect the activity of EFGR, the receptor involved in cell growth. Using mice, they discovered that EGFR is significantly more active at night (when GC levels are low), and less active during the day (when GC levels are high).
EGFR stimulates not only normal cell growth, but also the growth and spread of cancer cells. Having discovered this basic relationship between EFGR and GC, researchers next wanted to explore the possible effects of targeting cancer treatments using this new information. Using mice with a form of cancer influenced by EFGR, researchers gave the mice a cancer-drug that works by inhibiting EFGR. They administered the drug at different times throughout the mice's circadian day and night. Researchers discovered significant differences in tumor size after treatment. Mice treated during sleeping hours showed much smaller tumors than mice treated during waking hours.
These results suggest that the varying levels of GC, which rise and fall in a circadian rhythm, are involved in the degree of tumor growth in cancers that involve EFGR. The findings also suggest that aligning cancer treatment with the right circadian timing -- in this case during sleep, when GC levels are lowest -- may enhance the effectiveness of the treatment.
These findings are preliminary, and need further testing and examination in follow-up research. But they represent a potentially significant step forward in our understanding of one way 24-hour circadian rhythms may influence cancer growth -- and how we might time delivery of anti-cancer therapies to maximize their impact.
Science has been pursuing an understanding of the relationship between circadian rhythms and cancer for some time. Increasingly, evidence indicates that disruption to circadian rhythms -- and a lack of sufficient sleep -- may increase the risk of cancer occurring, and may contribute to more aggressive forms of the disease:
• There's evidence that poor quality, fragmented sleep compromises the immune system's ability to fight cancer, enabling tumor growth to become more aggressive. In one study, mice with cancer than experienced disrupted sleep for four weeks showed dramatically larger tumor growth than mice that were allowed to sleep normally. Researchers further traced the more aggressive tumor growth in mice to changes in immune system cells, which turned the cells from cancer fighters to actually helping cancer cells to grow.
• Research also links moderate and severe obstructive sleep apnea with significantly higher risks for cancer. These studies showed people with sleep apnea developing cancer at rates 2-4 times higher than people without sleep apnea. Mortality rates for people with cancer and sleep apnea are also shown to be higher than for people without sleep apnea.
There are so many important reasons to protect normal circadian function, and to make high quality sleep a daily priority. Our increasing understanding of the circadian influence over cancer is yet another very good one. As this latest study suggests, we may find that circadian timing has an important role to play in battling back against cancer as well.
Michael J. Breus, PhD
The Sleep Doctor™