胶质母细胞瘤（GBM）是成人最常见的原发性脑肿瘤。过去30年，GBM治疗方案一直相同，并且尽管采用了积极的多模式治疗，但仅略微延长了生存时间。愈来愈好的GBM生物学知识和其基因组分析全面阐明了GBM的异质性，有助于更有效的分子分类和创新的靶向治疗方法的开发。本文报告了免疫疗法和靶向治疗的所有值得注意的创新，并提供了有关当今试验设计的见解，包括与免疫肿瘤药物和目标组合的组合疗法。GBM分子异质性和脑解剖特征极大地限制了药物的有效性。尽管如此，对于GBM未来的研究和药物开发来说，革新性治疗策略给出了刺激性的见解，如多特异性“现成”的CAR-T治疗、溶瘤病毒治疗和自体树突状细胞疫苗接种。靶向治疗的临床试验的令人失望的结果主要是由于信号通路和生物过程之间复杂的干扰导致药物耐药性，因此未来发展组合疗法和多模式治疗至关重要。

Glioblastoma (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.This 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.GBM 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.