For years scientists have believed that glioblastoma (GBM), the deadliest form of brain cancer, stayed within the walls of the skull, but a new study challenges that belief. Scientists at Montefiore Einstein Comprehensive Cancer Center (MECCC) and Albert Einstein College of Medicine have revealed that GBM actually erodes parts of the skull and changes the bone marrow within it, affecting immune balance and response. GBM is a rare, invasive and aggressive cancer that rapidly grows in the spinal cord or brain and is resistant to most interventions including radiation, surgery and chemotherapy.
Using advanced imaging on mice and human patients, the researchers discovered that the tumor eats away at parts of the skull while also damaging brain tissue. Skull thinning and erosion were particularly noticeable around the sutures, where bones meet. As the skull wears down, the bone marrow inside begins to change and its balance gets altered.
There are tiny bone channels that the tumor sends signals through causing the bone marrow to make inflammatory immune cells and less protective ones, such as T cells and B cells. These inflammatory cells travel from the bone marrow to the brain fueling the tumors to grow and create a feedback loop that continues to affect the skull and immune defense.
The discovery shows that GBM can manipulate the body’s immune response by changing what happens within the bone marrow in the skull, meaning that brain cancer is not just a local but a systematic illness. The cancer spreads beyond the brain’s borders and reshapes the bone marrow to its advantage.
These findings raise questions about implications for treatments due to their interaction with the body if the adverse effects are worth the risk. Scientists have tested drugs to prevent bone loss, finding that this stopped skull erosion but allowed the tumors to become more aggressive via the feedback loop in the bone marrow.
In some cases the same medications also affect the body’s normal immune defense. Suggesting that when treating GBM cannot only focus on the brain but must consider the broader effects on bone and immunity to avoid unintended consequences.
Every year around 15,000 people in the United States are diagnosed with GBM, according to the National Cancer Institute, most live only about 15 months after diagnosis. This study will change the way doctors view the disease instead of being a confined brain problem, but as an illness that affects multiple systems in the body. By studying the connection, scientists aim to use the knowledge to develop interventions that stabilize bone marrow and lessen infection while addressing bone erosion.
