Scientists have uncovered surprising new details about glioblastoma, the most aggressive form of brain cancer. This deadly disease doesn’t just target the brain—it also erodes the skull, reshapes the bone marrow inside it, and disrupts the body’s immune defenses.
A research team from the Montefiore Einstein Comprehensive Cancer Center and Albert Einstein College of Medicine led this breakthrough study. They published their findings in the journal Nature Neuroscience, revealing how glioblastoma spreads its influence beyond the brain tissue.
“Glioblastoma is notoriously tough to beat,” said Jinan Behnan, an assistant professor in neurological surgery and microbiology and immunology at Einstein, who served as the study’s lead author. “Our discovery shows it interacts with the immune system, which might explain why current treatments—treating it like a localized problem—keep falling short. This could pave the way for smarter therapies.”
For patients facing glioblastoma, time is critical. Standard care, which includes surgery, chemotherapy, and radiation, gives a median survival of just 15 months. Now, this research highlights how the cancer messes with the skull’s inner workings. Like other bones in the body, the skull holds marrow where immune cells and blood cells develop.
In experiments with mice carrying two types of glioblastoma tumors, the team used advanced imaging to spot clear signs of damage. The tumors chewed away at the skull bones, particularly along the sutures—the seams where bones connect. This kind of erosion sets glioblastoma apart from other issues like strokes, regular brain injuries, or even cancers elsewhere in the body.
The pattern held true in humans too. CT scans of glioblastoma patients showed thinner skull areas in the same spots as seen in the mice, pointing to a consistent effect across species.
These erosions create more and wider channels linking the brain to the skull marrow. Researchers believe this lets the cancer send signals that overhaul the immune environment in the marrow. In the skull marrow, glioblastoma ramps up genes that crank out inflammatory immune cells. But in the femur’s marrow (in the thigh bone), it shuts down genes needed for other key immune cells, weakening defenses overall.
The study also tested potential fixes. FDA-approved drugs like zoledronic acid and denosumab, often used to fight osteoporosis and prevent bone loss, did stop the skull erosion. That’s promising at first glance. However, zoledronic acid actually sped up tumor growth in one glioblastoma type. Worse, both drugs interfered with anti-PD-L1 immunotherapy, which normally boosts tumor-killing T cells and helps fight the cancer.
This twist underscores a key challenge in brain cancer treatment: blocking one problem might unleash another. As experts dig deeper into glioblastoma’s sneaky ways of evading the immune system, they hope to develop targeted strategies that tackle the disease head-on without unintended side effects.
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