Sathe Shaunak, Li Qi, Jung Jinkyu, Wu Jing
Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Cancers (Basel). 2025 Sep 19;17(18):3062. doi: 10.3390/cancers17183062.
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.
高级别胶质瘤是侵袭性原发性脑肿瘤，通常是致命的。它们的特点是生长迅速、对治疗耐药，并且肿瘤内部和肿瘤之间存在显著的异质性。越来越多的证据表明，线粒体作为能量产生、细胞凋亡调节和代谢重塑所必需的动态细胞器，是胶质瘤进展和治疗耐药的关键驱动因素。因此，这些见解引发了人们对线粒体导向疗法的日益浓厚的兴趣。本综述强调了胶质瘤独特的代谢特征和线粒体过程，概述了靶向线粒体功能的基本原理。我们讨论了线粒体靶向疗法的最新进展，重点关注酪蛋白溶解蛋白酶P（ClpP）激动剂作为弥漫性中线胶质瘤（DMG）治疗的一项突破。此外，我们还讨论了线粒体代谢与表观遗传调控之间的致病联系，以及破坏这种相互作用的潜在治疗益处。
