Notes from the Lab: How Gliomas Disrupt Brain Function - and a Potential Way to Reverse It

The Gabriele Bartoli Brain Tumor Laboratory

Led by Peter D. Canoll, MD, PhD and Jeffrey N. Bruce, MD, we are a multidisciplinary group of researchers and clinicians dedicated to the care of patients with brain tumors, primarily glioblastoma (GBM), the most common and aggressive malignant primary brain tumor. Our lab studies the cellular and molecular mechanisms of gliomagenesis, immune responses to brain tumors, and the development of therapies for brain tumor patients.

The cancer problem we are solving

Gliomas are aggressive brain tumors that damage surrounding brain tissue as they grow, causing life-altering neurological symptoms like seizures, cognitive problems, and difficulty with memory and language. Much of the field of cancer neuroscience research has focused on how brain activity helps tumors grow by sending signals directly to glioma cells. 

However, less attention has been paid to the other side of this relationship: how the tumor itself damages the healthy brain cells around it. While researchers have known for a long time that gliomas disrupt normal brain function, exactly how this happens and whether this damage is reversible has remained unclear. Understanding and targeting these changes could lead to new treatments that can help reduce seizures, memory and thinking deficits, and other neurological symptoms caused by gliomas.

The research

"Glioma-induced alterations in excitatory neurons are reversed by mTOR inhibition," (Awarded Herbert Irving Comprehensive Cancer Center's Trainee Associate Member Paper of the Year in 2026)

What this new research uncovers 

Using mouse models of glioma, our team examined what happens to excitatory neurons (brain cells that trigger electrical impulses to pass messages through the brain) as they become surrounded by a growing tumor. We found that these tumor-associated neurons undergo important changes in the genes they use, their physical structure, and how they communicate with one another. 

We discovered that glioma cells activate a key signaling pathway called mTOR in nearby neurons. This disrupts normal communication between brain cells, causing them to lose important connections and become overactive. These tumor-associated neurons also demonstrate heightened and disorganized responses to sensory stimulation and fire together in abnormal patterns similar to those seen in seizures. At the same time, this abnormal brain activity can also fuel tumor growth, creating a harmful cycle between the brain and the cancer. 

Importantly, our evidence demonstrates that these tumor induced changes are not permanent. A single dose of the experimental mTOR inhibitor AZD8055 reversed many of these effects within hours, restoring more normal brain cell function and communication.  

While more research is needed, our findings suggest that some of the brain changes caused by gliomas may be reversible, indicating a degree of plasticity present in the tumor microenvironment, opening the door to new ways to treat symptoms such as seizures and cognitive problems. 

For patients, this could have important implications. The neurological symptoms of glioma can be just as life-altering as the tumor itself, yet current treatments often do not address them well. Our findings suggest that treatments targeting the healthy neurons surrounding the tumor, not just the tumor cells themselves, could offer a new therapeutic strategy. We also found that communication between neurons and glioma cells goes both directions: the tumor alters brain activity, and that abnormal activity, in turn, helps the tumor grow. Breaking this harmful cycle could improve both quality of life and future treatment strategies.

Next steps 

Building on these findings, we are working to better understand how glioma cells communicate with healthy brain cells. By identifying the signals that allow this communication, we hope to develop more targeted cancer treatments. Our sensory simulation model allows us to precisely control and measure brain cell activity as a tumor grows, helping us see how this activity affects not only glioma cells but also other cells that surround and support the tumor. Ultimately, the goal is to turn these discoveries into clinical trials that improve treatment for the neurological symptoms caused by glioma, including seizures, memory and thinking problems, and other changes that can have a major impact on daily life.