文章：

靶向线粒体治疗高级别胶质瘤

Targeting the Mitochondria in High-Grade Gliomas

原文发布日期：19 September 2025

DOI: 10.3390/cancers17183062

类型: Article

开放获取: 是

英文摘要：

High-grade gliomas are aggressive primary brain tumors and often fatal. They are characterized by rapid growth, treatment resistance, and significant heterogeneity both within and between tumors. A growing body of evidence highlights the mitochondria, dynamic organelles essential for energy production, apoptosis regulation, and metabolic rewiring, as a critical driver in glioma progression and treatment resistance. As a result, these insights have sparked growing interest in mitochondrial-directed therapies. This review highlights the distinct metabolic features and mitochondrial processes of glioma, outlining the rationale for targeting mitochondrial function. We discuss recent advances in mitochondrial-targeted therapies, with a focus on caseinolytic protease P (ClpP) agonism as a breakthrough in the treatment of diffuse midline glioma (DMG). Moreover, we discuss the pathogenic link between mitochondrial metabolism and epigenetic regulation, and the potential therapeutic benefit of disrupting this interaction.

摘要翻译： 

高级别胶质瘤是侵袭性原发性脑肿瘤，常具有致命性。其典型特征包括快速生长、治疗抵抗性以及肿瘤内部与肿瘤间显著的异质性。越来越多的证据表明，作为能量生成、凋亡调控和代谢重编程关键细胞器的线粒体，是驱动胶质瘤进展和治疗抵抗的核心因素。这些发现引发了针对线粒体靶向治疗日益增长的研究兴趣。本综述重点阐述胶质瘤独特的代谢特征与线粒体生物学过程，系统论述靶向线粒体功能的治疗理论基础。我们讨论了线粒体靶向治疗的最新进展，特别聚焦酪蛋白水解蛋白酶P（ClpP）激动剂作为弥漫性中线胶质瘤（DMG）治疗领域的突破性进展。此外，本文还探讨了线粒体代谢与表观遗传调控之间的致病性关联，以及破坏这种相互作用可能带来的治疗获益。

原文链接：

Targeting the Mitochondria in High-Grade Gliomas