It’s news to no one that your body works differently when you’re awake and when you’re sleeping. But could the different states also affect how your body processes certain life-saving drugs? Researchers, reporting Friday in the journal Nature Communications, found that when it comes to cancer drugs, the answer may be yes.
Researchers at the Weizmann Institute of Science discovered—by happy accident—that some of the body’s molecular functions during the day may interfere with the effectiveness of certain cancer medication. Specifically, they found that the normal day-time production of some steroid hormones in the body actually inhibited the work of epidermal growth factor (EGF) receptors—which are the proteins targeted by a class of anti-cancer drugs. Tumor cells plant these receptors on their surfaces to attract nutrients that help them survive and grow. Drugs, including the breast cancer agent lapatinib, can block these receptors on tumors, and such medications are a popular way to treat breast cancers expressing epidermal growth factor.
But Yosef Yarden, a professor in the department of biological regulation, and his team found that when the tumor cells simultaneously bind to something else—such as steroid hormones—the EGF receptors are less active, making drugs like lapatinib less potent.
The findings are still preliminary, but there is other evidence that the day-night cycle may be a potentially important factor in determining cancer treatment dosing in coming years. Some studies showed, for example, that when the 24-hour rest and activity cycle is broken metabolically, and the EGF receptors aren’t given enough time to be active, certain tumors in animals grow two to three times faster.
“The study developed out of a mistake. We accidentally omitted a synthetic steroid…from the medium in which we routinely grow mammary gland cells,” Yarden wrote in an email response to TIME. “And we noticed that the cells acquired a faster rate of migration when we followed them under a microscope.”
Intrigued, they turned to mice to answer some more questions. Knowing that steroid levels peak during the day and drop off during sleep, Yarden and his colleagues wondered whether the timing of anti-tumor drugs would affect tumor growth. So they gave a group of mice with breast cancer tumors lapatinib at different times over a 24-hour period and tracked any differences in the size and growth of the tumors.
Indeed, the mice given the drug while they slept showed significantly smaller tumors after seven days than those who received the drug during the day. Yarden suspects that the lower levels of steroid hormones circulating at night allows more of the EGF-targeting drug to hone in on its receptors on the tumor cells and inhibit their growth. Not only that, but the tumors in the mice taking the drug at night looked different; they showed less blood vessel infiltration which meant they were less robust.
Does that mean it’s better to get cancer therapy at night? So far, the results only apply to animal models, and to cancers driven by EGF. More work needs to be done, but if it’s validated, shifting therapies to just before bed “seems logical,” says Yarden. Especially since drugs like lapatinib come in pill form, so it would be relatively easy to take medications before turning in rather than in the morning.
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