By Avigayil Kadesh

Serendipity has yielded a remarkable breakthrough in the understanding of how cancerous tumors grow – and a more effective way to fight them.

Researchers at Israel’s Weizmann Institute of Science discovered that malignant tumors grow faster at night. The unexpected finding suggests that administering certain treatments in time with the body’s day-night cycle could boost their efficiency, as they reported in Nature Communications in August 2014.

A team led by Mattia Lauriola, a postdoctoral fellow in the biological regulation research group of Prof. Yosef Yarden, working together with Prof. Eytan Domany of the physics of complex systems department, started out with the intention to investigate “the remarkable reliance of human cancers on hormone-like proteins called growth factors,” according to Yarden.
 
“We noted that a steroid hormone called glucocorticoid potently inhibits one outcome of the growth factors, namely the ability to migrate across tissue barriers. Hence, we decided to study the underlying mechanism,” he explains.

Receptors – protein molecules on the cell’s surface or within cells – normally take in biochemical messages secreted by other cells and pass them on into the cell’s interior. The scientists focused on two: the epidermal growth factor receptor, EGFR, which promotes the growth and migration of cells; and a receptor that binds to glucocorticoid, otherwise known as the “stress hormone” because it is released in higher levels in response to stressful situations, rapidly bringing the body to a state of full alert.

In the experiment, Lauriola and Yarden found that cell migration promoted by EGFR is suppressed when the stress hormone receptor is bound to its steroid messenger.
 
Since the steroid levels peak during waking hours and drop off during sleep, the scientists wondered how this might affect the second receptor, EGFR. Checking the levels of this activity in mice, they found that this receptor is much more active during sleep than during waking hours.

Better to give cancer drugs at night
 
The researchers were intrigued by how this difference might affect the growth of cancer cells.

Using mouse models of cancer, they administered Lapatinib, a new-generation drug used to treat breast cancer by inhibiting EGFR. The mice were divided into groups that were given 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 indicate that the rise and fall in the levels of glucocorticoid over the course of 24 hours actually hinder or enable the growth of the cancerous cells.
 
The obvious conclusion is that it could be more efficient to administer certain anticancer drugs at night.

“It seems to be an issue of timing,” says 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.