Emerging therapies for glioblastoma: current state and future directions

Glioblastoma (GBM) is the most common high-grade primary malignant brain tumor with an extremely poor prognosis. Given the poor survival with currently approved treatments for GBM, new therapeutic strategies are urgently needed. Advances in decades of investment in basic science of glioblastoma are rapidly translated into innovative clinical trials, utilizing improved genetic and epigenetic profiling of glioblastoma as well as the brain microenvironment and immune system interactions. Following these encouraging findings, immunotherapy including immune checkpoint blockade, chimeric antigen receptor T (CAR T) cell therapy, oncolytic virotherapy, and vaccine therapy have offered new hope for improving GBM outcomes; ongoing studies are using combinatorial therapies with the aim of minimizing adverse side-effects and augmenting antitumor immune responses. In addition, techniques to overcome the blood-brain barrier (BBB) for targeted delivery are being tested in clinical trials in patients with recurrent GBM. Here, we set forth the rationales for these promising therapies in treating GBM, review the potential novel agents, the current status of preclinical and clinical trials, and discuss the challenges and future perspectives in glioblastoma immuno-oncology.