Researchers at the UVA Comprehensive Cancer Center, Virginia’s first National Cancer Institute (NCI)-designated comprehensive cancer center, have identified a molecule that blocks the gene responsible for glioblastoma (GBM), raising hopes that it could become a much-needed new treatment for the deadliest brain cancer.
The results of their study, funded by the National Institutes of Health (NIH) and the Ben & Catherine Ivy Foundation, and published in the January 28, 2026, Science Translational Medicine.
Researcher Hui Li, PhD, previously identified the ‘oncogene’ responsible for glioblastoma, a cancer for which there are no treatments that extend survival beyond a few months. In his follow-up work, published in Science Translational Medicine, Li reports the identification of a small molecule that blocked the gene’s activity in both cell samples and lab mice. In mice, the molecule proved effective without unwanted or harmful side effects.[1]
“While more work needs to be done before the molecule could be used as a treatment in people, the results so far are promising and suggest the compound could prevent the invasive cancer from spreading through the brain,” Li explained.
A fast-growing disease
“Glioblastoma is a devastating disease. Essentially, no effective therapy exists,” said Li, of the University of Virginia School of Medicine’s Department of Pathology.
“What’s novel here is that we’re targeting a protein that GBM 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.”
Overdrive
Glioblastoma is a fast-growing form of brain cancer that is almost always deadly. Typical survival after diagnosis is only about 15 months, and more than 14,000 Americans are diagnosed every year. Treatment options include surgery, but the way the cancer proliferates through the brain makes it difficult to remove. Other treatments include chemotherapy and radiotherapy, but they only extend the survival for a few months. These treatments can also greatly affect quality of life, so some patients opt out of treatment altogether.
The difficulty of treating the disease and the limited benefits of the available treatments mean new options are desperately needed. Li’s line of research, he hopes, could produce a more effective alternative.
In 2020, Li first identified the oncogene responsible for glioblastoma. That gene, known as the actin-binding protein advillin (AVIL), normally helps cells maintain their size and shape. But the researchers noted that this gene is overexpressed, oncogenic, and necessary for tumorigenesis in GBM, and that it can be driven into overdrive by various factors. This causes cancer cells to form and spread.
At the time, the researchers found that blocking the gene’s activity could completely eliminate glioblastoma cells in lab mice, without affecting healthy cells. But the lab technique they used to determine that is unsuitable for use in people. That put them on the hunt for a molecule that could stop the gene’s harmful effects.
Their pursuit has confirmed AVIL’s role in glioblastoma. The researchers found that the protein produced by the gene is rarely found in healthy human brains but is abundant in patients with glioblastoma.
The scientists used a technique called ‘high-throughput screening’ to quickly and efficiently evaluate many compounds for their potential to block AVIL activity. The molecule they have found appears to affect only tumor cells, sparing healthy brain tissue. Further, the molecule can cross the brain’s protective barrier that keeps out many potential treatments for neurological diseases.
As a treatment, the compound could be taken by mouth, like any other prescription pill, the researchers say.
More research needed
Before the compound becomes available to patients, much additional research will be needed to optimize the molecule for use in people. If all goes according to plan, the resulting drug would then be tested extensively in human volunteers before the federal Food and Drug Administration decides whether it is sufficiently safe and effective to be offered as a treatment.
While there is much more work to be done, Li and his colleagues are excited by the promise of their latest findings.
“GBM patients desperately need better options. Standard therapy hasn’t fundamentally changed in decades, and survival remains dismal,” he said.
“Our goal is to bring an entirely new mechanism of action into the clinic — one that targets a core vulnerability in glioblastoma biology,” Li concluded.
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Note:* Li has founded a company, AVIL Therapeutics, to develop AVIL inhibitors. He and Xie have also obtained a patent related to the approach.
Reference
[1] Xie Z, Janczyk PŁ, Cornelison R, Lynch S, Glowczyk-Gluc M, Leifer B, Wang Y, Hahn P, Dooley JD, Fierti A, Shi X, Zhang Y, Li T, Wang Q, Zhang Z, Marrah L, Koehler A, Mandell JW, Hilinski M, Li H. A first-in-class small-molecule inhibitor targeting AVIL exhibits safety and antitumor efficacy in preclinical models of glioblastoma. Sci Transl Med. 2026 Jan 28;18(834):eadt1211. doi: 10.1126/scitranslmed.adt1211. Epub 2026 Jan 28. PMID: 41604465.
Featured image: Brain Cancer Chromosomes. Chromosomes prepared from a malignant glioblastoma visualized by spectral karyotyping (SKY) reveal an enormous degree of chromosomal instability, a hallmark of cancer. Created by Thomas Ried, 2014. Photo courtesy: © 2019 – 2026 National Institute of Health. Licensed Under the Unsplash License.
DOI
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