Malhotra Dinky, Gabrani Reema
Department of Biotechnology, Jaypee Institute of Information Technology, A-10, Sector 62, Noida, UP, 201309, India.
Mol Biol Rep. 2025 Jan 22;52(1):146. doi: 10.1007/s11033-025-10242-7.
Metabolic reprogramming stands out as a defining characteristic of cancer, including glioblastoma (GB), enabling tumor cells to overcome growth and survival challenges in adverse conditions. The dysregulation of metabolic processes in GB is crucial to its pathogenesis, influencing both tumorigenesis and the disease's invasive tendencies. This altered metabolism supplies essential energy substrates for uncontrolled cell proliferation and also creates an immunosuppressive microenvironment, complicating conventional therapies. A comprehensive understanding of the complexities of metabolic dysregulation in carbohydrate, amino acid, lipid and nucleotide pathways in GB holds promise for effective therapeutic interventions. Key metabolic enzymes, transporters, and signaling pathways and mitochondrial metabolism have been examined for their roles in GB pathology and their possible therapeutic potential. Addressing these metabolic targets has shown efficacy in preclinical models and is currently being evaluated in clinical trials. Combination therapies that exploit metabolic vulnerabilities alongside conventional treatments hold the promise of improving patient outcomes. This review explores the dynamic interplay between glioblastoma's aggressiveness and altered metabolism, offering insights into potential therapeutic strategies. Moreover, this review discusses the recent advancements in drug development aimed at targeting these dysregulated metabolic pathways.
代谢重编程是癌症（包括胶质母细胞瘤，GB）的一个决定性特征，使肿瘤细胞能够在不利条件下克服生长和生存挑战。GB中代谢过程的失调对其发病机制至关重要，影响肿瘤发生和疾病的侵袭倾向。这种改变的代谢为不受控制的细胞增殖提供了必需的能量底物，还创造了一个免疫抑制微环境，使传统疗法变得复杂。全面了解GB中碳水化合物、氨基酸、脂质和核苷酸途径中代谢失调的复杂性有望实现有效的治疗干预。关键代谢酶、转运体、信号通路和线粒体代谢已被研究其在GB病理学中的作用及其潜在的治疗潜力。针对这些代谢靶点已在临床前模型中显示出疗效，目前正在临床试验中进行评估。利用代谢弱点与传统治疗相结合的联合疗法有望改善患者预后。本综述探讨了胶质母细胞瘤的侵袭性与代谢改变之间的动态相互作用，为潜在治疗策略提供见解。此外，本综述讨论了针对这些失调代谢途径的药物开发的最新进展。
