Tumors may grow faster at night, say Weizmann scientists

Scientists found that hormone that keeps us alert also suppresses metastasis.

By JUDY SIEGEL-ITZKOVICH
Cancer cells (photo credit: REUTERS)
Cancer cells
(photo credit: REUTERS)
Weizmann Institute of Science researchers recently discovered that cancer grows and spreads faster while its patients are asleep at night, meaning that administrating certain drugs in accordance with patients’ biological clocks may boost their efficiency.
Dr. Mattia Lauriola, a postdoctoral fellow in the research group of Prof. Yosef Yarden of the Rehovot institute’s biological regulation department, carried out the research that has just been published in the Nature Communications journal.
Lauriola and Yarden worked on the project with Prof. Eytan Domany of the complex systems physics department and focused on two particular receptors.
The first, the epidermal growth factor receptor (EGFR), promotes the growth and migration of cells, including cancer cells. The second receptor binds to a steroid hormone called a glucocorticoid (GC).
Glucocorticoids play a role in maintaining the body’s energy levels during the day, as well as the metabolic exchange of materials. It is often called the stress hormone because its levels rise in stressful situations, rapidly bringing the body to a state of full alert.
With multiple receptors, the cell receives all sorts of messages at once, and some of them can take precedence over others.
In the experiment, Lauriola and Yarden found that cell migration – the activity promoted by the EGF receptor – is suppressed when the GC receptor is bound to its steroid messenger.
Since the steroid levels peak during waking hours and drop off during sleep, the scientists asked how this might affect the EGFR. Checking the levels of this activity in mice, they found that there was a significant difference: The receptor is much more active during sleep and dormant during waking hours.
To find out how relevant these findings are for cancers, particularly those that use the EGF receptors to grow and spread, the scientists gave new generation cancer drug Lapatinib to mouse models of cancer. This drug, used to treat breast cancer, is designed to inhibit EGFR and thus to prevent the growth and migration of the cancer cells.
In the experiment, they gave the mice the drug at different times of day. The results revealed significant differences between the sizes of tumors in the different groups of mice, depending on whether they had been given the drug during sleep or waking hours.
The experimental findings suggest that it is indeed the rise and fall in the levels of the GC steroids over the course of 24 hours that hinder or enable the growth of the cancer. The scientists’ conclusion was that it could be more efficient to administer certain anti-cancer drugs at night.
“It seems to be an issue of timing,” said Yarden. “Cancer treatments are often administered in the daytime, just when the patient’s body is suppressing the spread of the cancer on its own. What we propose is not a new treatment, but rather a new treatment schedule for some of the current drugs.”