胶质母细胞瘤是一种罕见且高度致命的脑癌，在治疗耐药性方面提出了重大挑战，并且成人和儿童患者的生存率都很低。尽管技术革命推动了脑癌研究的进步，但将我们对胶质母细胞瘤发病机制的理解转化为改善的临床结果仍然是一个未得到满足的关键需求。本综述强调了受体酪氨酸激酶信号通路、表观遗传机制和代谢功能在胶质母细胞瘤肿瘤发生和治疗耐药中的复杂作用。我们还讨论了过去二十年来探索针对这些途径的靶向疗法的广泛努力。抗体-毒素偶联物或 CAR T 细胞疗法等新兴治疗方法通过特异性靶向胶质母细胞瘤细胞表面的蛋白质而提供了潜力。蛋白质靶向治疗和免疫治疗的联合策略为未来的临床研究展现了巨大的前景。此外，深入了解起源细胞在胶质母细胞瘤治疗反应中的作用有可能推动精准医学方法的发展。应对这些挑战对于改善胶质母细胞瘤患者的治疗效果和迈向更有效的精准治疗至关重要。© 2023。四川大学华西医院。

Glioblastoma, a rare, and highly lethal form of brain cancer, poses significant challenges in terms of therapeutic resistance, and poor survival rates for both adult and paediatric patients alike. Despite advancements in brain cancer research driven by a technological revolution, translating our understanding of glioblastoma pathogenesis into improved clinical outcomes remains a critical unmet need. This review emphasises the intricate role of receptor tyrosine kinase signalling pathways, epigenetic mechanisms, and metabolic functions in glioblastoma tumourigenesis and therapeutic resistance. We also discuss the extensive efforts over the past two decades that have explored targeted therapies against these pathways. Emerging therapeutic approaches, such as antibody-toxin conjugates or CAR T cell therapies, offer potential by specifically targeting proteins on the glioblastoma cell surface. Combination strategies incorporating protein-targeted therapy and immune-based therapies demonstrate great promise for future clinical research. Moreover, gaining insights into the role of cell-of-origin in glioblastoma treatment response holds the potential to advance precision medicine approaches. Addressing these challenges is crucial to improving outcomes for glioblastoma patients and moving towards more effective precision therapies.© 2023. West China Hospital, Sichuan University.