胶质母细胞瘤（GBM）是最常见的恶性原发性成人脑肿瘤。尽管采用包括手术切除、替莫唑胺 (TMZ) 治疗和放射治疗在内的标准护理治疗，GBM 患者的预后仍然很差，五年生存率为 5%。通过治疗，中位生存时间为 14 个月，这表明迫切需要新的、更有效的疗法。谷氨酰胺分解是细胞将谷氨酰胺转化为 ATP 的代谢途径，对于 GBM 细胞的生存至关重要，也是公认的治疗目标。谷氨酰胺通过谷氨酰胺分解补充三羧酸（TCA）循环中间体。谷氨酰胺分解的第一步，即谷氨酰胺脱氨基作用，可以通过谷氨酰胺酶 1 (GLS) 或谷氨酰胺酶 2 (GLS2) 进行。然而，越来越清楚的是，这些酶在 GBM 中具有相反的功能。 GLS 诱导谷氨酰胺脱氨基，从而以致癌方式发挥作用，而 GLS2 具有非酶促肿瘤抑制功能，但在 GBM 中受到抑制。在这篇综述中，我们探讨了谷氨酰胺分解在 GBM 中的重要作用以及 GLS 和 GLS2 的相反作用。此外，我们还详细讨论了 GLS2 新发现的可针对 GBM 的非酶功能。最后，我们考虑了基于对 GLS 和 GLS2 在 GBM 中相反作用的理解而出现的治疗方法。版权所有 © 2024。由 Elsevier B.V. 出版。

Glioblastoma (GBM) is the most common malignant primary adult brain tumor. Despite standard-of-care treatment, which consists of surgical resection, temozolomide (TMZ) treatment, and radiotherapy, the prognosis for GBM patients remains poor with a five-year survival rate of 5 %. With treatment, the median survival time is 14 months, suggesting the dire need for new, more effective therapies. Glutaminolysis, the metabolic pathway by which cells can convert glutamine to ATP, is essential for the survival of GBM cells and represents a putative target for treatment. Glutamine replenishes tricarboxylic acid (TCA) cycle intermediates through glutaminolysis. The first step of glutaminolysis, the deamination of glutamine, can be carried out by either glutaminase 1 (GLS) or glutaminase 2 (GLS2). However, it is becoming increasingly clear that these enzymes have opposing functions in GBM; GLS induces deamination of glutamine, thereby acting in an oncogenic fashion, while GLS2 has non-enzymatic, tumor-suppressive functions that are repressed in GBM. In this review, we explore the important role of glutaminolysis and the opposing roles of GLS and GLS2 in GBM. Further, we provide a detailed discussion of GLS2's newly discovered non-enzymatic functions that can be targeted in GBM. We conclude by considering therapeutic approaches that have emerged from the understanding of GLS and GLS2's opposing roles in GBM.Copyright © 2024. Published by Elsevier B.V.