Chemo may be more effective depending on time of day, WVU research finds

MORGANTOWN, W.Va. — Chemotherapy may be more effective at certain times of the day, according to a study by a researcher at the University of West Virginia.

WVU Today reported that the blood-brain barrier prevents foreign substances from entering the brain, which is good for toxins and germs, but makes treating brain tumors trickier. By protecting the brain from things that could harm it, the blood-brain barrier also blocks chemotherapy that would help it.

William Walker, Postdoctoral Fellow, WVU Department of Neuroscience (WVU Photo)

William Walker, a researcher at the WVU School of Medicine, is investigating whether the blood-brain barrier is more likely to admit chemotherapy drugs at different times of the day.

His study was funded by the National Institutes of Health and shows that the blood-brain barrier is dynamic rather than static and suggests that properly timed chemotherapy treatments may better reach the tumors they target.

“We are not the first to show that chrono-chemotherapy is beneficial, but we are the first to show that it is beneficial in the treatment of brain metastases,” said Walker, a postdoctoral fellow in the Department of Neuroscience.

His findings have been published in “Frontiers in Oncology”.

Walker and his colleagues administered chemotherapy to mice with breast cancer, which had traveled to the brain.

Some of the mice received the treatments in daylight, when the mice, being nocturnal, are generally at rest. The other animals received them in the dark, a setting that more closely resembles the active period of the mice.

The researchers found that the chemotherapy they gave during the dark phase killed more brain tumor cells than those given during the light phase.

Dark-phase chemotherapy treatments were also more successful in delaying neurological symptoms, like odd walking habits and loss of muscle control.

They also increased the median survival rate by about 20%.

“In all of our projects, we try to ask ourselves, ‘If we see an effect at the molecular level, does that translate? Is there functional relevance? said Walker. “To some degree, it might be unnecessary to increase the amount of chemotherapy in the brain tumor at some point, but we don’t see any functional difference, we don’t improve survival, or we don’t improve changes in neurological deficit So these results were great to see.

Questions remain. Does the human blood-brain barrier also fluctuate? If so, is he more responsive to chemotherapy during the day or at night? Do the fluctuations reflect the fact that humans are diurnal creatures (more active during the day) or are they an effect of light exposure itself?

Randy Nelson, chair, WVU Department of Neuroscience;  Director, WVU Center for Foundational Neuroscience Research and Education (WVU Photo)
Randy Nelson, chair, WVU Department of Neuroscience; Director, WVU Center for Foundational Neuroscience Research and Education (WVU Photo)

“These are the questions that William Walker will address when he leaves this lab and launches his own,” said Randy Nelson, chair of the Department of Neuroscience, director of the WVU Center for Basic Neuroscience Research and Education, and mentor. of Walker.

Typically, people on chemotherapy receive their treatments during the day, during regular office hours, but “if it turns out that people are more like flies and the blood-brain barrier opens at night , so maybe it’s the best time to give chemo,” Nelson said.

“Chrono-chemotherapy has been shown to be beneficial for years — in terms of peripheral cancer — but for some reason this basic science isn’t being translated into clinical practice,” Walker said. “I think this is an important step. That’s my goal in starting my own lab: to try to raise awareness so that we can actually translate some of the basic science that we see into clinical practice to improve patient outcomes.

To read Walker’s full study, click here. WVU Today also included notes on animal research and ethics which can be viewed here.


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