The most common type of brain tumor in children, pilocytic astrocytoma (PA), accounts for approximately 15% of all pediatric brain tumors. While typically not life-threatening, these tumors can disrupt normal brain development and function due to unchecked cell growth. Current treatments primarily focus on removing the tumor cells, but recent research suggests that non-cancerous cells, such as nerve cells, also play a significant role in tumor formation and growth, opening the door to novel treatment approaches.
Scientists have long recognized that glutamate, a nerve cell signaling chemical, can promote cancer growth throughout the body. However, understanding the precise mechanisms and how to inhibit them has remained elusive. Now, an interdisciplinary team at Washington University School of Medicine in St. Louis has uncovered how glutamate regulates pediatric brain tumor growth. Their findings, published on September 1 in the journal Neuron, reveal that PA cells hijack proteins on cell surfaces known as glutamate receptors, reprogramming them to send signals that increase cell growth.
Breakthrough in Understanding Tumor Growth
The research team discovered that drugs blocking these glutamate receptors, including memantine—an approved treatment for dementia and Alzheimer’s—reduced human pediatric brain tumor growth in mice. This discovery points to a potential new treatment opportunity for these tumors.
“With these kinds of pediatric brain tumors, we just don’t have that many tools in our toolbox for treating patients,” said senior author Dr. David Gutmann, the Donald O. Schnuck Family Professor of Neurology at WashU Medicine. “The potential to repurpose drugs already in use for other neurological disorders means we may have another trick up our sleeves for treating patients.”
New Uses for Familiar Tools
Glutamate, a neurotransmitter, is a molecule used by nerve cells, including brain neurons, to communicate. In their quest to understand how glutamate aids brain tumor growth, Dr. Gutmann and first author Dr. Corina Anastasaki collaborated with various departments at WashU Medicine to analyze samples of surgically removed PAs. They found unusually high levels of glutamate receptors in these PA cells.
Testing revealed that glutamate increased PA cell numbers by initiating a chain reaction within the tumor cells, prompting them to divide. These findings suggest that tumor cells exploit normal brain-cell interactions to spur their growth.
“This novel mechanism for tumor growth combines two normal but unconnected brain processes—growth and electrical signaling—in an aberrant way,” Dr. Anastasaki explained. “Now that we’ve figured out how these cells work and grow, the sky’s the limit for exploring other neurotransmitters and communication avenues between neurons and cancer cells.”
Implications for Future Treatments
The study’s implications are significant. By inhibiting glutamate receptors in mice with PAs, either through medication or genetic alteration, researchers observed reduced tumor growth. This suggests a promising opportunity to repurpose glutamate receptor-targeting drugs like memantine for treating PAs.
Dr. Gutmann emphasized the need for clinical trials to determine the safety and efficacy of such medications in children with brain tumors. “This study provides compelling preclinical data to look at medications that are otherwise safe and approved for other neurological conditions,” he said. “That could enable new therapeutic approaches and help minimize damage to a child’s developing brain by reducing engagement between brain cells and tumor cells.”
Looking Ahead
The research, partially funded by grants from the National Institutes of Health and other organizations, marks a significant step forward in understanding pediatric brain tumors. As the team continues to explore the role of neurotransmitters in tumor growth, their findings could lead to innovative treatments that leverage existing drugs, potentially transforming the landscape of pediatric oncology.
Washington University School of Medicine, a leader in biomedical research and patient care, remains at the forefront of such groundbreaking studies. With a robust research funding portfolio and a commitment to innovation, WashU Medicine continues to push the boundaries of medical science, offering hope and new possibilities for patients worldwide.
