Gatto Lidia, Di Nunno Vincenzo, Ghelardini Anna, Tosoni Alicia, Bartolini Stefania, Asioli Sofia, Ratti Stefano, Di Stefano Anna Luisa, Franceschi Enrico
Nervous System Medical Oncology Department, IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy.
Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy.
Biomedicines. 2024 Nov 28;12(12):2730. doi: 10.3390/biomedicines12122730.
Drugs targeting mitochondrial energy metabolism are emerging as promising antitumor therapeutics. Glioma treatment is extremely challenging due to the high complexity of the tumor and the high cellular heterogeneity. From a metabolic perspective, glioma cancer cells can be classified into the oxidative metabolic phenotype (mainly depending on mitochondrial respiration for energy production) and glycolytic phenotype or "Warburg effect" (mainly depending on glycolysis). Herein, we reviewed the function of novel bio-active molecules targeting oxidative phosphorylation (OXPHOS), mitochondrial membrane potential and mitochondrial dynamics. These molecules exhibit intriguing preclinical and clinical results and have been proven to be promising candidates to be further developed for glioma therapy. However, despite these initial encouraging results, it is imperative to rigorously assess the side effects of these metabolic drugs, which have a non-negligible toxicity profile.
靶向线粒体能量代谢的药物正成为有前景的抗肿瘤疗法。由于肿瘤的高度复杂性和高细胞异质性,胶质瘤治疗极具挑战性。从代谢角度来看,胶质瘤癌细胞可分为氧化代谢表型(主要依靠线粒体呼吸产生能量)和糖酵解表型或“瓦伯格效应”(主要依靠糖酵解)。在此,我们综述了靶向氧化磷酸化(OXPHOS)、线粒体膜电位和线粒体动力学的新型生物活性分子的功能。这些分子展现出了有趣的临床前和临床结果,并且已被证明是有前景的、可进一步开发用于胶质瘤治疗的候选药物。然而,尽管有这些初步的鼓舞人心的结果,但必须严格评估这些代谢药物的副作用,其毒性不容忽视。