Scientists Found a Way to Kill the Deadliest Brain Cancer That Has No Cure

Brain cancer does not play fair. Among its worst forms, one stands out for its speed, its resistance to treatment, and its ability to rob patients of time. For decades, doctors have had almost nothing new to offer. Surgery, radiation, and a chemotherapy drug that adds only a few extra months have been the standard approach since the early 2000s. But a research team at the University of Virginia may have just changed the equation. They found a molecule that targets the one protein glioblastoma cells depend on to survive, and it kills those cells without harming the healthy brain around them. If the science holds up in human trials, patients could one day take this treatment as a pill. And the story of how they got here starts with a discovery made five years ago that nobody had been able to act on until now.

What is Glioblastoma?

Each year, about 14,000 people in the United States receive a glioblastoma diagnosis. It is the most common and most aggressive form of brain cancer. Patients who receive treatment survive an average of 12 to 18 months. Without treatment, the timeline shrinks even further. Only about 5% of patients are still alive five years after diagnosis.

What makes glioblastoma so devastating is not just its speed. It is how few options exist. Surgery can remove visible tumor tissue, but glioblastoma cells spread into surrounding brain tissue in ways that make complete removal almost impossible. Radiation slows regrowth. Temozolomide, the most commonly prescribed chemotherapy drug for the disease, adds an average of just a few months of survival and comes with serious side effects.

Hui Li, a pathology researcher at the University of Virginia School of Medicine, put it plainly: glioblastoma is a devastating disease, and no effective therapy exists. Standard treatment has not changed in decades, and survival remains grim.

A Hidden “Kill Switch” Found in 2020

Before you can kill a cancer, you need to know what keeps it alive. In 2020, Li and his team made a discovery that cracked open a new direction for glioblastoma research. They identified an oncogene called AVIL (short for advillin) that drives the growth and survival of glioblastoma cells.

An oncogene is a gene that, when activated or overexpressed, pushes normal cells toward becoming cancerous. AVIL turned out to be a powerful one. When the team silenced it in lab models, glioblastoma cells died. Tumor growth stopped in mice. And healthy brain cells were left untouched. Li called AVIL glioblastoma’s Achilles’ heel, a single point of weakness that the cancer depends on to survive.

But there was a catch. Silencing the gene in the lab used a technique called RNA interference (RNAi), which works well in controlled experiments but is not practical for treating real human patients. You cannot deliver RNAi into a living brain the way you can prescribe a drug. So while the 2020 discovery identified the target, the team still needed a weapon that could actually hit it inside a human body.

Five Years Later: A Molecule That Fits the Lock

Finding a drug that blocks a specific protein is a bit like finding a key that fits one lock out of millions. Li’s team screened large numbers of small molecules to find one that could bind to the AVIL protein and shut down its activity. After extensive testing, they landed on what they call Compound A.

Compound A locks onto the AVIL protein and blocks its interaction with actin, a structural protein that AVIL uses to carry out its cancer-promoting functions. When Compound A binds to AVIL, it triggers a chain reaction that mirrors what happened when the gene was silenced in the 2020 study. Two downstream targets involved in cell growth and cancer progression, FOXM1 and LIN28B, were both suppressed. Gene expression changes across the entire cell matched what researchers saw with RNAi, confirming that Compound A works through the same biological pathway.

Tumor cells with high levels of AVIL were more sensitive to the compound. Meanwhile, healthy astrocytes and neural stem cells were largely spared. In other words, the molecule attacked the cancer and left normal brain tissue alone.

Crossing the Blood-Brain Barrier: A Major Hurdle Cleared

One of the biggest challenges in treating brain cancer is getting a drug past the blood-brain barrier. Your brain is protected by a tightly sealed network of blood vessels that blocks most substances from entering brain tissue. Many promising cancer drugs fail not because they cannot kill tumor cells, but because they cannot reach them.

Compound A cleared that hurdle. When given orally to mice, the molecule crossed the blood-brain barrier and reached tumor tissue inside the brain. That finding alone is a significant step, because it means this treatment could potentially be delivered as a simple pill rather than through invasive procedures like direct brain injection or implanted drug-delivery devices.

Five Mouse Models, Zero Toxic Side Effects

To test Compound A thoroughly, Li’s team ran experiments across five different mouse models of glioblastoma. Some mice carried tumors implanted inside the brain. Others carried patient-derived tumors, meaning real human glioblastoma tissue grown in mice, including tumors that were resistant to temozolomide.

In all five models, Compound A reduced tumor growth. And even at higher doses, the researchers saw no signs of treatment toxicity. Organ tissue remained healthy. Blood work came back normal. Body weight held steady.

For a field where most treatments cause heavy collateral damage, a compound that kills cancer cells and spares the rest of the body represents a rare and welcome finding.

Why AVIL Is Such a Good Target

Not all oncogenes make good drug targets. Some are expressed in too many healthy tissues, making it dangerous to block them. Others play roles in multiple cancers but are not consistent enough to build a reliable therapy around.

AVIL stands out for several reasons. It is expressed at very high levels across all four molecular subtypes of glioblastoma and across four distinct cellular states within tumors, including glioblastoma stem cells. Stem cells are particularly important because they are often responsible for regrowth after treatment. Many drugs can shrink a tumor but fail to kill the stem cells hiding within it, which leads to recurrence.

AVIL expression also remains high in tumors that have become resistant to temozolomide. Since temozolomide resistance is one of the main reasons glioblastoma treatment fails, a drug that works even in resistant tumors fills a gap that current treatments cannot.

On the safety side, healthy brain tissue shows little to no AVIL expression. Previous research showed that silencing AVIL did not affect normal astrocytes or neural stem cells. So the target exists almost exclusively in cancer cells, which is what every oncologist hopes to find.

Li’s team compared AVIL to ALK, another well-known oncogene active across several cancer types. Early (mostly unpublished) data suggest AVIL may also play a role in pediatric sarcoma and some common solid tumors, raising the possibility that a drug targeting AVIL could one day extend beyond brain cancer.

From Lab Bench to Pill Bottle: What Comes Next

Compound A is not ready for patients yet. Before it reaches a pharmacy shelf, it must clear years of additional testing, starting with optimization of the drug’s chemical properties and eventually moving into Phase I clinical trials in humans.

Li’s lab is already deep into that work. His team has created more than 160 chemical derivatives of Compound A, with several lead compounds showing potency at nanomolar concentrations. That means these refined versions can block AVIL at extremely low doses, a promising sign for both effectiveness and safety in humans.

Li has said his goal is to move a candidate compound into Phase I clinical studies within two years. If that timeline holds, glioblastoma patients could have access to an entirely new class of treatment within the next several years.

Why Patients Cannot Wait

Glioblastoma does not give patients the luxury of time. A 15-month median survival leaves almost no room for trial and error. Families face devastating timelines from the moment of diagnosis, and the treatment options available today were developed over 20 years ago.

Every year, thousands of patients go through surgery, radiation, and chemotherapy knowing that the best available medicine will extend their lives by only a few months. Against that backdrop, a compound that targets a tumor-specific protein, crosses the blood-brain barrier, works against drug-resistant tumors, and can be taken orally represents something rare in glioblastoma research: genuine hope grounded in real evidence.

As Li and his team wrote, their goal is to bring an entirely new mechanism of action into the clinic, one that targets a core weakness in glioblastoma biology. For patients and families who have had almost nothing new to hope for in two decades, that goal cannot arrive soon enough.

My Personal RX on Protecting Your Brain Health

Brain cancer is not always preventable, but supporting your brain’s overall health reduces your risk for many neurological conditions and keeps your mind sharp as you age. I tell my patients that brain health starts with what you eat, how you sleep, and how well you manage stress and inflammation. Your brain consumes about 20% of your body’s energy, so the fuel you give it matters. Here is what I recommend:

1. Prioritize Deep, Restorative Sleep: Your brain clears toxic waste proteins during deep sleep through the glymphatic system. Sleep Max contains magnesium, GABA, 5-HTP, and taurine to calm your mind, balance neurotransmitters, and promote restorative REM sleep so your brain can repair itself each night.
   
2. Know Which Supplements Your Brain Needs: After age 40, your body absorbs fewer nutrients that your brain depends on for energy, focus, and protection. Download my free guide, The 7 Supplements You Can’t Live Without, to learn which supplements fill those gaps, which “healthy” foods may be misleading you, and how to spot quality products.
   
3. Move Your Body to Boost Brain Blood Flow: Exercise increases oxygen delivery to your brain and stimulates the release of brain-derived neurotrophic factor (BDNF), a protein that supports neuron growth and survival. Aim for at least 30 minutes of moderate activity most days of the week.
   
4. Reduce Sugar and Processed Food Intake: High sugar diets promote inflammation and oxidative stress in brain tissue. Replace processed snacks with whole foods like berries, leafy greens, nuts, and fatty fish to feed your brain cells what they actually need.
   
5. Limit Alcohol Consumption: Even moderate alcohol intake can shrink brain volume over time. Cutting back supports clearer thinking, better sleep, and reduced inflammation throughout your nervous system.
   
6. Challenge Your Brain Daily: Mental stimulation builds cognitive reserve, which helps your brain stay resilient against disease. Read, learn a new skill, play strategy games, or engage in creative hobbies that require focus and problem-solving.
   
7. Manage Chronic Stress Before It Damages Your Brain: Prolonged stress elevates cortisol, which can shrink the hippocampus and weaken memory over time. Practice daily stress management through breathwork, meditation, or time in nature.
   
8. Talk to Your Doctor About Persistent Neurological Symptoms: Do not ignore chronic headaches, vision changes, memory problems, or personality shifts. Early evaluation can catch treatable conditions before they progress and give you the best chance at a positive outcome.

Source: 

Xie, Z., Janczyk, P. Ł., Cornelison, R., Lynch, S., Glowczyk-Gluc, M., Leifer, B., Wang, Y., Hahn, P., Dooley, J. D., Fierti, A., Shi, X., Zhang, Y., Li, T., Wang, Q., Zhang, Z., Marrah, L., Koehler, A., Mandell, J. W., Hilinski, M., & Li, H. (2026). A first-in-class small-molecule inhibitor targeting AVIL exhibits safety and antitumor efficacy in preclinical models of glioblastoma. Science Translational Medicine, 18(834), eadt1211. https://doi.org/10.1126/scitranslmed.adt1211