The diagnosis of glioblastoma often bears one of the grimmest prognosis for patients. But a new research discovery may offer new hope for the most complete destruction of this cancer yet. The approach involves targeting a specific protein that stops cancer cells from dividing as well as spreading –in effect, dealing glioblastoma a potent two-in-one punch
Glioblastoma multiforme (GBM) is the most common and deadly form of primary brain cancer. In GBM, malignant glial cells form vast networks of tendrils throughout the brain, making it nearly impossible to surgically remove all the cancerous tissues. Dubbed as the “octopus tumor,” GBMs can evade even the most aggressive surgeries, chemotherapies, and radiotherapies, leaving patients with a five-year survival rate of less than 10 percent. Patients are in desperate need of better alternatives or supplementary treatments to beat this notoriously deadly cancer.
In observing how the GBM cancer cells invade healthy tissues, researchers at the Medical Research Council (MRC) Clinical Sciences Centre based at Imperial College London noticed something unique. They found that under normal conditions, healthy blood vessels produce a protein called ephrin-B2 to sequester damaged cells and prevent those cells from spreading. However, when the damaged cells turned cancerous, they made their own ephrin-B2, an override mechanism that allows them to now invade into blood vessels and nearby tissues. Cancerous cells with more ephrin-B2 also continued to divide at faster rates, effectively multiplying the damages they inflict on the brain.
After identifying ephrin-B2, the team next tried to block this protein in a mouse model of GBM. Indeed, the team found that without access to their own ephrin-B2 supply, the cancer cells couldn’t spread. Blocking ephrin-B2 also turned off the signals telling the cells to divide, thus the number of the cancer cells also plummeted.
"The ephrin-B2 protein is complex but in this case it works in our favor. By blocking one molecule we affect two key aspects of tumors; their ability to divide and their ability to invade. It could be a combined therapy in one," said Simona Parrinello, senior study author.
Patients diagnosed with GBM often have an average of 15 months of survival. Part of the reason why this cancer is so aggressive and resistant to therapy is its propensity to spread through the brains’ blood vessels. This makes it nearly impossible for surgeons to completely find and remove all traces of the cancer – inevitably, some cancer will remain and take over once again.
"These types of brain tumors are not only the most common but also the most difficult to treat. The MRC's investment in high quality brain tumor research is advancing our knowledge of how the disease works and could help in the search for a more effective treatment,” said Adam Babbs, program manager for cancer research at the MRC. Indeed, ephrin-B2 renews the hope of eliminating GBM in a swift and complete manner that’s not feasible with just surgery alone.
Additional source: Medical Research Council (MRC)