Brain cancer remains one of the most difficult forms of cancer to treat, but researchers at the are making meaningful strides to change that. From reprogramming cancer cells to uncovering hidden mechanisms of resistance, UCLA scientists are pursuing a wide range of approaches to attack glioblastoma and other deadly brain tumors.
The need for more effective treatments for brain tumors like glioblastoma is imperative. The average lifespan of someone diagnosed with glioblastoma is just 12 to 15 months, and only about 5% of people diagnosed with the disease are alive five years after their diagnosis.
“While glioblastoma remains a formidable challenge, these breakthroughs, which include novel combination therapies, next-generation organoid models, precision medicine strategies, and first-in-human vaccine trials, bring real hope,” said , chair of neurosurgery at the David Geffen School of Medicine at UCLA and director of the . “Each new discovery gets us closer to improving survival and quality of life for patients facing this devastating disease.”
Here’s a look at some of the most recent discoveries that are helping to advance more effective and targeted treatment strategies for glioblastoma and other aggressive brain cancers:
Reprogramming brain cancer cells to halt tumor growth
, professor of radiation oncology at the David Geffen School of Medicine at UCLA, and his laboratory have developed a promising new treatment strategy to treat glioblastoma by combining radiation therapy with a plant-derived compound called forskolin. Radiation alone is known to kill many cancer cells, but it can also temporarily make glioblastoma stem cells more flexible, or adaptable, providing an opportunity to alter their identity. The team discovered that by timing the delivery of forskolin during this window, they could push these adaptable cancer cells to become neuron-like or microglia-like that don’t divide uncontrollably or regenerate tumors. This reprogramming approach effectively halts the cancer’s ability to grow and spread. found when tested in mice, the addition of forskolin to radiation significantly slowed tumor growth in mice and, in some cases, led to long-term tumor control.
Insight into how blood vessel-tumor interactions fuel glioblastoma can help lead to new treatment strategies
A newly identified protein called endocan, produced by blood vessel cells in brain tumors, may be a key driver of glioblastoma growth and treatment resistance. In a recent study, a team of researchers, led by , director of the UCLA Intellectual and Developmental Research Center and professor of psychiatry, pediatrics and molecular and medical pharmacology, found that endocan activates the PDGFRA receptor on tumor cells, helping the cancer thrive and resist radiation therapy. By blocking this interaction with the drug ponatinib, they were able to slow tumor growth and improve radiation response in lab models. highlight endocan’s role in shaping the tumor’s invasive edges, areas that often survive surgery, and suggest that targeting this protein could lead to more effective treatments for this aggressive and deadly brain cancer.
Combining genetic and functional profiling to predict glioblastoma treatment response
, scientist , professor of molecular and medical pharmacology, and his team developed a new approach that combines genetic and functional profiling to better predict how glioblastoma responds to treatment. By analyzing both a tumor’s DNA and how its cells react to therapies in real time, the team identified a protein called BCL-XL as a key player in helping cancer cells evade death. Using this insight, they tested a drug called ABBV-155 that targets BCL-XL and found it significantly shrank tumors in lab models when paired with standard treatments. This precision medicine strategy could lead to more effective, personalized therapies for glioblastoma patients.
A personalized cancer vaccine to tackle aggressive brain tumors in adolescents and young adults
In an effort to combat one of the most lethal forms of pediatric brain cancer, a team of researchers led by , director of the Pediatric Brain Tumor Program at UCLA Health, launched a to evaluate the safety and effectiveness of a cancer vaccine targeting H3 G34-mutant diffuse hemispheric glioma, a highly aggressive brain tumor that is typically found in adolescents and young adults. The vaccine uses the patient’s own dendritic cells to target tumor-specific neoantigens caused by disrupted RNA regulation. The goal is to train the immune system to recognize and destroy cancer cells more effectively. Researchers hope the approach will improve survival and lead to more precise, immune-based treatments for this challenging disease.
Immune-boosting agent supercharges personalized vaccine
A team of researchers led by Liau and , professor of neurosurgery and of molecular and medical pharmacology, found that combining a dendritic cell cancer vaccine with poly-ICLC, an immune-stimulating agent, significantly enhances the immune response in patients with malignant glioma, a fast-growing and hard-to-treat brain tumor. , patients receiving the combination therapy showed stronger T cell activity and increased interferon response, improving the dendritic cells’ ability to fight the brain tumor more effectively than the vaccine alone. The findings suggest that poly-ICLC may boost the vaccine’s potency and offer a promising new strategy for treating gliomas. A is already underway to explore this combination further.
Using organoids to uncover the mechanisms behind treatment resistance in glioblastoma
UCLA researchers , assistant professor of medicine and biological chemistry, and , assistant professor of neurosurgery, are developing advanced brain organoid models, which are model versions of the human brain grown in a lab dish, to better understand how glioblastoma develops and spreads. By implanting tumor samples into stem cell-derived organoids that closely mimic the human brain, the team is studying how different cell types within the tumor interact with their environment. aims to uncover the lineage and evolution of glioblastoma cells and identify new strategies to disrupt tumor growth and improve treatment outcomes.
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