New Delhi– Glioblastoma, the most lethal form of brain cancer, affects more than just the brain itself, according to a new study. Researchers at the Montefiore Einstein Comprehensive Cancer Center (MECCC) and Albert Einstein College of Medicine have found that the disease can erode the skull, alter skull marrow composition, and disrupt the body’s immune response.
The findings, published in Nature Neuroscience, represent the first evidence that glioblastoma interacts with the skull and immune system — a discovery that could help explain why current treatments have been largely unsuccessful.
“Our discovery that this notoriously hard-to-treat brain cancer interacts with the body’s immune system may help explain why current therapies — all of them dealing with glioblastoma as a local disease — have failed, and it will hopefully lead to better treatment strategies,” said corresponding author Jinan Behnan, Assistant Professor of Neurological Surgery and Microbiology & Immunology at Einstein.
Glioblastoma patients typically survive about 15 months following standard treatment with surgery, chemotherapy, and radiation.
The study revealed that glioblastomas cause erosion in skull bones, particularly along sutures where skull plates fuse. Using advanced imaging in mice with glioblastoma, researchers observed these erosions, which appeared unique to malignant intracranial tumors and did not occur with strokes, other brain injuries, or systemic cancers. CT scans of human patients showed similar skull thinning in the same areas.
These erosions expanded skull-to-bone channels, which scientists believe may allow glioblastoma to transmit signals to skull marrow, reshaping its immune environment. In skull marrow, glioblastoma activated genes that increased inflammatory immune cells, while in femur marrow, it suppressed genes needed to produce several types of immune cells.
The team also tested U.S. FDA-approved osteoporosis drugs zoledronic acid and denosumab, which prevent bone loss and successfully halted skull erosion. However, zoledronic acid accelerated tumor growth in one glioblastoma type, and both drugs blocked the benefits of anti-PD-L1, an immunotherapy designed to enhance tumor-fighting T cells.
The study underscores the complexity of glioblastoma and the need for therapies that address its systemic effects rather than treating it solely as a localized brain tumor. (Source: IANS)
