Glioblastoma, considered the most aggressive form of brain cancer, is now shown to extend its impact beyond the brain.
Researchers from the Montefiore Einstein Comprehensive Cancer Centre (MECCC) and Albert Einstein College of Medicine have provided the first evidence that the disease erodes the skull, alters the composition of skull marrow, and interferes with the immune system.
The findings, published in Nature Neuroscience, also suggest that treatments designed to prevent bone loss may unintentionally worsen tumour progression, complicating therapeutic strategies for patients.
“Our discovery that this notoriously hard-to-treat brain cancer interacts with the body’s immune system may explain why current therapies have failed, and it will hopefully lead to better treatment strategies,” said Dr Jinan Behnan, Assistant Professor of Neurological Surgery and Microbiology & Immunology at Einstein.
Currently, patients receiving the standard treatment of surgery, chemotherapy, and radiation face a median survival of just 15 months. This new evidence underscores the urgent need for therapies that address glioblastoma as more than a localised brain disease.
The skull, like other bones, contains marrow that produces immune and blood cells. Using advanced imaging on mice with two glioblastoma types, the researchers observed significant erosion along the sutures where skull bones fuse.
Such erosions, absent in strokes, other brain injuries, or even systemic cancers, appear unique to glioblastoma and malignant intracranial tumours. CT scans of glioblastoma patients mirrored these findings, showing reduced skull thickness in the same regions.
Immune System Disruption
The study found that skull erosion widened skull-to-bone channels, likely enabling glioblastoma to send signals that altered the skull marrow’s immune activity.
In the skull marrow, the cancer boosted genes producing inflammatory immune cells. By contrast, in femur marrow, glioblastoma suppressed genes essential for generating several immune cell types.
This dual effect highlights how the cancer manipulates the body’s immune response differently depending on the site, making effective treatment more challenging.
The researchers also tested anti-osteoporosis drugs already approved by the US FDA, such as zoledronic acid and denosumab, which can stop bone loss.
While these drugs halted skull erosion, zoledronic acid accelerated tumour growth in one glioblastoma type. Moreover, both drugs blocked the effectiveness of anti-PD-L1, an immunotherapy that boosts cancer-fighting T cells.
The findings raise urgent questions about how glioblastoma interacts with the bone and immune systems. By uncovering this hidden dimension of the disease, scientists hope to develop therapies that not only target the brain but also address its wider systemic effects.
This breakthrough study provides fresh direction for researchers and offers renewed hope for improving outcomes in one of the most lethal cancers.
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