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Researchers at West Virginia University (WVU) have found that the effectiveness of chemotherapy may change with the time of day that it is administered.
Chemotherapy is a type of cancer treatment in which two or more anti-cancer drugs are used. It is a part of a standard cancer treatment plan that defines drugs to be used, frequency and duration of treatment and their dosage.
During the chemotherapy process, however, the blood-brain barrier (BBB) prevents drugs from entering the brain. The blood-brain barrier (BBB) is a network of tissues and blood vessels made up of closely spaced cells. It helps keep harmful substances from reaching the brain. It allows some substances such as oxygen, water and carbon dioxide to pass into the brain. This is a good physiological process when it comes to infectious agents like bacteria, viruses and toxins. But, it also blocks anticancer drugs from entering the brain, thus making the chemotherapy process ineffective in treating brain tumors.
William Walker, at WVU, investigated whether the BBB allows the movement of anti-cancer drugs at different times of the day. His study showed that the blood-brain barrier is dynamic and not static. He also suggested that chemotherapy given at the proper time can treat tumors better.
“We are not the first ones to show that chrono-chemotherapy is beneficial, but we’re the first to show that it’s beneficial in the treatment of brain metastasis,” said Walker, a postdoctoral fellow in the Department of Neuroscience.
Walker and his team delivered anti-cancer drugs into the mice with breast cancer that had metastatized or traveled to their brains. Some of the mice were given chemotherapy in daylight. And the rest of them received treatment in the dark. As mice are nocturnal animals, their brains are active in the dark.
The researchers found that the chemotherapy treatment given in the dark destroyed most of the tumor cells as compared to mice receiving drugs in the day. They also discovered that this treatment delayed neurological symptoms such as abnormal walking patterns, loss of muscle control in these mice.
Moreover, this had also increased the average survival rate of the mice by about 20 percent.
“In all our projects we try to ask, ‘If we see an effect molecularly, does that translate? Is there a functional relevance to it?” said Walker. “To an extent, it might be pointless if we increase the amount of chemotherapy within the brain tumor at a certain time, but we don’t see any functional difference, we don’t improve survival, or we don’t improve changes in a neurological deficit. So, these results were great to see.”
In concern to the human blood-brain barrier, some questions remained answered. For instance, does the human blood-brain barrier fluctuate? If it fluctuates, is it more receptive to anti-cancer drugs in the night or day? Do the fluctuations show that human brains are active in the day or they are just a result of light exposure?
“Those are the questions, William Walker will be looking into when he leaves this lab and start his own,” said Randy Nelson, chair of the Department of Neuroscience and Walker’s mentor.
Generally, cancer patients receive treatment in the daytime- but “if it’s the case that people are more like flies, and the blood-brain barrier opens up at night, then that might be the best time to give chemo,” said Nelson.
“Chrono-chemotherapy has been shown to be beneficial for years- in terms of peripheral cancer- but for some reason that basic science is not being translated into clinical practice,” said Walker. “I think that’s 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.”
The findings are published in the journal Frontiers in Oncology.