A potential breakthrough in the fight against glioblastoma, the deadliest form of brain cancer, is emerging from UVA Cancer Center. University of Virginia scientists, with support from the National Institutes of Health and the Ben & Catherine Ivy Foundation, have identified a small molecule that blocks a key cancer-driving gene, raising hopes for a new treatment where options remain devastatingly limited.
UVA researcher Hui Li found the molecule successfully shut down the gene’s activity in cells and lab mice without harmful side effects, according to research published in Science Translational Medicine. While more work is needed before it can be tested in people, the early results are encouraging.
“Glioblastoma is a devastating disease. Essentially, no effective therapy exists,” said Li, of the UVA School of Medicine’s Department of Pathology. “What’s novel here is that we’re targeting a protein that (glioblastoma) cells uniquely depend on, and we can do it with a small molecule that has clear in vivo activity. To our knowledge, this pathway hasn’t been therapeutically exploited before.”
Researcher Hui Li of the UVA School of Medicine’s Department of Pathology emphasizes the urgent need for new glioblastoma treatments, saying his team’s goal is to bring “an entirely new mechanism of action into the clinic.” (Contributed photo)
Glioblastoma is an aggressive form of brain cancer that is almost always fatal. Patients typically survive only about 15 months after diagnosis, and more than 14,000 Americans learn they have the disease each year. Surgery is often part of treatment, but the cancer’s tendency to spread through brain tissue makes it difficult to remove completely. Chemotherapy and radiation can add only a few months of survival and may significantly affect quality of life, leading some patients to forgo treatment altogether.
In 2020, Li identified the oncogene responsible for glioblastoma. Known as AVIL, the gene normally helps cells maintain their size and shape, but researchers found it can be pushed into overdrive, triggering cancer cells to form and spread.
At the time, researchers found shutting down the gene’s activity could eliminate glioblastoma cells in lab mice without harming healthy cells. But the method they used couldn’t be applied to people, prompting a search for a molecule that could safely block the gene’s effects.
That work has further confirmed AVIL’s role in the disease. The protein produced by the gene is rarely present in the healthy human brain, but is abundant in glioblastoma patients.
