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William Walker, a researcher at West Virginia University School of Medicine, is investigating whether the blood-brain barrier is more susceptible to chemotherapy drugs at different times of the day
.
His research—funded by the National Institutes of Health—shows that the blood-brain barrier is dynamic, not static, suggesting that properly timed chemotherapy can better reach their target tumors
.
"We are not the first to show that chronochemotherapy is beneficial, but we are the first to show that it is beneficial for treating brain metastases," said Walker, a postdoctoral researcher in the Division of Neuroscience
.
His findings were published in the journal Frontiers in Oncology
.
Walker and his colleagues injected chemotherapy drugs into mice with breast cancer that had entered the brain
.
Some of these mice were treated in daytime conditions, when mice were usually nocturnal and at rest
.
Other animals received them in the dark, an environment closer to the active period in mice
The researchers found that chemotherapy administered during the dark period killed more brain tumor cells than chemotherapy administered during the light period
.
Dark-phase chemotherapy also did a better job of delaying neurological symptoms, such as strange walking patterns and loss of muscle control
.
They also improved median survival by about 20 percent
.
"In all of our projects, we try to ask ourselves, 'If we see an effect molecularly, is it translated? Is it functionally relevant?'" Walker said
.
"In a way it might be pointless if we increased the amount of chemotherapy in the brain tumor at a given time, but we didn't see any functional difference, we didn't improve survival, or we didn't improve neurological function Changes in defects
The problem still exists
.
Does the human blood-brain barrier also fluctuate? If so, are they more susceptible 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 the light itself?
“These are the kinds of questions that William Walker left this lab to start his own research,” said Randy Nelson, chair of the neuroscience department and director of the Center for Basic Neuroscience Research and Education at West Virginia University and Walker’s mentor
.
Typically, people receiving chemotherapy are treated during the day -- during normal business hours -- but "if the situation is that people are more like flies and the BBB is open at night, then this may be the best time to do chemotherapy.
," Nelson said
.
"Chronotherapy has been shown to be beneficial in peripheral cancers for many years, but for some reason the basic science has not been translated into clinical practice," Walker said
.
"I think that's an important step
Journal Reference :
William H.
