TUMORS MIGHT GROW FASTER AT NIGHT
They emerge at night,
while we sleep unaware, growing and spreading out as quickly as they can. And
they are deadly. In a surprise finding that was recently published in Nature Communications, Weizmann Institute of Science researchers showed that
nighttime is the right time for cancer to grow and spread in the body. Their
findings suggest that administering certain treatments in time with the body's
day-night cycle could boost their efficiency.
This finding arose out
of an investigation into the relationships between different receptors in the
cell -- a complex network that we still do not completely understand. The
receptors -- protein molecules on the cell's surface or within cells -- take in
biochemical messages secreted by other cells and pass them on into the cell's
interior. The scientists, led by Dr. Mattia Lauriola, a postdoctoral fellow in
the research group of Prof. Yosef Yarden of the Weizmann Institute's Biological
Regulation Department, working together with Prof. Eytan Domany of the Physics
of Complex Systems Department, 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 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 these
messages 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 second receptor -- EGFR. Checking the levels of this
activity in mice, they found that there was a significant difference: This
receptor is much more active during sleep and quiescent during waking hours.
How relevant are these
findings for cancers, particularly those which use the EGF receptors to grow
and spread? To find out, the scientists gave Lapatinib -- one of the new
generation of cancer drugs -- 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 conclusion, say
the scientists, 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. What we propose is not a new treatment, but
rather a new treatment schedule for some of the current drugs."
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