Glioblastoma treatment slowly moves toward change: novel druggable targets and translational horizons in 2022

IntroductionGlioblastoma (GBM) is the most common primary brain tumor in adults. GBM treatment options have been the same for the past 30 years and have only modestly extended survival, despite aggressive multimodal treatments. The progressively better knowledge of GBM biology and a comprehensive analysis of its genomic profile have elucidated GBM heterogeneity, contributing to a more effective molecular classification and to the development of innovative targeted therapeutic approaches.Areas coveredThis article reports all the noteworthy innovations for immunotherapy and targeted therapy, providing insights into the current advances in trial designs, including combination therapies with immuno-oncology agents and target combinations.Expert opinionGBM molecular heterogeneity and brain anatomical characteristics critically restrain drug effectiveness. Nevertheless, stimulating insights for future research and drug development come from innovative treatment strategies for GBM, such as multi-specific 'off-the-shelf' CAR-T therapy, oncolytic viral therapy and autologous dendritic cell vaccination. Disappointing results from targeted therapies-clinical trials are mainly due to complex interferences between signaling pathways and biological processes leading to drug resistance: hence, it is imperative in the future to develop combinatorial approaches and multimodal therapies.

Automated summary

"Immunotherapy and targeted therapy for glioblastoma" summarizes the recent advancements in immunotherapy and targeted therapy for glioblastoma, including trial designs and combination therapies with immuno-oncology agents and targeted treatments. The molecular heterogeneity of glioblastoma and anatomical characteristics of the brain limit the effectiveness of drugs, but new treatment strategies such as multi-specific CAR-T therapy, oncolytic viral therapy, and autologous dendritic cell vaccination show promise for the future.