Identifying adverse effects of chemotherapy on the brain will lead to chemo-brain interventions
The number of cancer survivors is rapidly increasing, due to significant advances in cancer treatments. However, many treatments result in long lasting cognitive impairments, which often interfere with a cancer survivor’s quality of life. The gradual effects of chemotherapy on the brain function—known as “chemo brain”—can lead to a decreased ability to concentrate, focus, recall important information, and solve complex problems. Dr. Rex Philpot, assistant professor in the department of Psychiatry and Behavioral Neuroscience at University of South Florida, is developing interventions that can treat and prevent these deficits, which will have a tremendous impact on life quality and workplace performance for cancer survivors.
Many cancer survivors live with cognitive impairments as a result of chemotherapy treatment, often without realizing their brain function has gradually changed. Because the effects of cancer interact with chemotherapy and produce effects that cancer drugs cannot produce alone, using animal tumor models is critical for identifying the mechanisms that cause these deficits and for developing effective treatments. Dr. Philpot uses animal models with naturally-occurring cancer, performing a long term evaluation of tumor development, treatment effectiveness, and relapse risk. Currently, he is focused on treating cancers with high survival rates resulting from chemotherapy, particularly breast cancer. As the animal models undergo chemotherapy, Dr. Philpot assesses its effects on cognitive function—including spatial memory, working memory, discrimination learning, and conditional learning—as well as the effects of his treatment intervention on cognition, tumor progression and the effectiveness of chemotherapy.
Dr. Philpot’s team includes a veteran pharmacologist, and Ph.D.’s and M.D.’s who specialize in chemotherapy-induced cognitive deficits in cancer survivors. As they explore innovative treatments and an intervention in novel animal models, they aim to improve the quality of life for cancer survivors by preventing or reversing resulting cognitive deficits.
Current research includes:
- Identifying the Efficacy of Multiple Cognitive Treatments - Several drugs have been developed for the treatment of cognitive deficits over the last twenty years. Dr. Philpot and his team have been testing these drugs—such as acetylcholinesterase inhibitors, nicotinic receptor agonists, and natural compounds—for their ability to improve cognitive function for those impaired by chemotherapy. These drugs have shown positive results in improving learning and memory. They are looking at acetylcholinesterase inhibitors, like donepezil, which has been tested in humans with chemo brain. When a patient takes this drug, it increases acetylcholine in various regions of the brain, binding to every type of sensitive acetylcholine receptor. Though it improves performance, negative side effects can occur because of the global activation of the brain.. Dr. Philpot and his team are exploring ways to activate only one type of acetylcholine receptor, which will result in improved benefits with less side effects. Using animal models, they are testing nicotinic receptor agonists that activate only one receptor subtype for that neurotransmitter and targeting specific brain regions involved in learning and memory.
- Testing an Intervention the Prevents the Impairment of Memory From Chemotherapy- When a patient has cancer, the cancer cells absorb basic nutrients to promote tumor growth. This deprives the rest of the body and brain of critical nutrients. As a result of testing nicotinic acetylcholine receptor drugs, Dr. Philpot developed a hypothesis about the mechanism by which cognitive deficits first occur. He and his team identified an intervention that prevents the impairment of spatial memory caused by the chemotherapeutic drugs used to treat breast cancer. To test this hypothesis, they greatly increased basic nutrients—which act as the building blocks for cells—in the diets of their animal models as they underwent chemotherapy. Animals given this diet rarely develop a cognitive deficit in response to chemotherapy. Dr. Philpot’s research indicates that increasing specific dietary nutrients while undergoing chemotherapy can prevent deficits in normal brain function and the breakdown of neurons. They have preliminary data that shows that this dietary intervention does not affect tumor growth or interfere with chemotherapy, but they need to assess the effectiveness of this intervention over a full dose range, assess the effects on other domains of cognition—including attention, working memory, and problem solving—and verify that there are no risks of increased tumor growth or decreased chemotherapy effectiveness. They also need to assess how this treatment interacts with other common forms of chemotherapy to ensure it’s safe to use in humans.
As a cognitive behavioral neuroscientist, Dr. Rex Philpot has been working in the field of animal behavior and cognition for decades. He has always been interested in the interface between biology and psychology; how biochemistry translates into thoughts, feelings, and motivations. He received his MA in psychology and Ph.D. in cognitive and neural sciences at University of South Florida. Dr. Philpot is highly experienced in neurochemistry and understanding brain pathways, animal behavior, and assessing motivation, desire, and various forms of cognitive function.
During his early career, Dr. Philpot made a personal observation about drug abuse that would lead into addiction studies. He had friends who used drugs when they were teenagers, and knew individuals who first started using drugs as adults. He developed a theory that drug use led to fundamentally different changes in the brain when used during the rapid development of the brain during adolescence. Using animal models, Dr. Philpot investigated the changes in neurotransmitters involved in memory, emotion, and pleasure—such as dopamine, serotonin, and norepinephrine—produced by drug abuse during different period of adolescent development and in adulthood.
He discovered that abusing drugs during the development of the adolescent brain increases the user’s risk for long term abuse. Conversely, those fundamental changes in brain circuitry do not occur if an individual doesn’t take drugs until later in life, decreasing their vulnerability. This catapulted his interest in the ways chemical exposure—such as drugs of abuse and chemotherapeutic agents—can result in fundamental changes in cognitive capacity, personality, and motivation. From his background in addiction research and studying the effects of nicotine, he learned that activation of the nicotinic receptor is beneficial for learning and memory. This knowledge would later bridge his work into cancer research.
About two and a half years ago, some of Dr. Philpot’s close friends were diagnosed with cancer and underwent chemotherapy. He felt the need to help in some way, which led to a major transition in his research. Upon studying cancer literature, Dr. Philpot learned of common cognitive conditions cancer survivors developed as a consequence of treatment. No one knew what caused them, or had developed any preventative treatment. He decided to devote part of his work to exploring ways to combat these deficits as they occur in cancer survivors. As he started rapidly making new observations and discoveries, his work in cancer studies moved forward, where he currently devotes much of his research. From studying the interactions between biology and psychology, Dr. Philpot is motivated to develop therapies that prevent or reverse adverse changes in brain function.