Malone Kyle, LaCasse Eric, Beug Shawn T
Apoptosis Research Centre, Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada.
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
Cell Oncol (Dordr). 2025 Apr;48(2):313-349. doi: 10.1007/s13402-024-01007-8. Epub 2024 Nov 6.
Glioblastoma is the commonest and deadliest primary brain tumor. Glioblastoma is characterized by significant intra- and inter-tumoral heterogeneity, resistance to treatment and dismal prognoses despite decades of research in understanding its biological underpinnings. Encompassed within this heterogeneity and therapy resistance are severely dysregulated programmed cell death pathways. Glioblastomas recapitulate many neurodevelopmental and neural injury responses; in addition, glioblastoma cells are composed of multiple different transformed versions of CNS cell types. To obtain a greater understanding of the features underlying cell death regulation in glioblastoma, it is important to understand the control of cell death within the healthy CNS during homeostatic and neurodegenerative conditions. Herein, we review apoptotic control within neural stem cells, astrocytes, oligodendrocytes and neurons and compare them to glioblastoma apoptotic control. Specific focus is paid to the Inhibitor of Apoptosis proteins, which play key roles in neuroinflammation, CNS cell survival and gliomagenesis. This review will help in understanding glioblastoma as a transformed version of a heterogeneous organ composed of multiple varied cell types performing different functions and possessing different means of apoptotic control. Further, this review will help in developing more glioblastoma-specific treatment approaches and will better inform treatments looking at more direct brain delivery of therapeutic agents.
胶质母细胞瘤是最常见且最致命的原发性脑肿瘤。胶质母细胞瘤的特征在于肿瘤内和肿瘤间存在显著的异质性，尽管数十年来一直在研究其生物学基础，但它对治疗具有抗性且预后不佳。这种异质性和治疗抗性中包含严重失调的程序性细胞死亡途径。胶质母细胞瘤重现了许多神经发育和神经损伤反应；此外，胶质母细胞瘤细胞由多种不同的中枢神经系统细胞类型的转化版本组成。为了更深入地了解胶质母细胞瘤中细胞死亡调控的潜在特征，了解在稳态和神经退行性疾病状态下健康中枢神经系统内的细胞死亡控制至关重要。在此，我们综述神经干细胞、星形胶质细胞、少突胶质细胞和神经元内的凋亡控制，并将它们与胶质母细胞瘤的凋亡控制进行比较。特别关注凋亡抑制蛋白，其在神经炎症、中枢神经系统细胞存活和胶质瘤发生中起关键作用。这篇综述将有助于将胶质母细胞瘤理解为由多种执行不同功能且具有不同凋亡控制方式的不同细胞类型组成的异质性器官的转化形式。此外，这篇综述将有助于开发更多针对胶质母细胞瘤的治疗方法，并将为寻求更直接的脑内治疗药物递送的治疗提供更好的信息。
