Yuxiao Chen, Jiachen Wang, Yanjie Lan, Shenglan Li, Yuji Wang, Wenbin Li
Department of Neuro-Oncology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Xuanwu Hospital (The First Clinical College of Capital Medical University), Beijing, China.
Front Pharmacol. 2024 Aug 22;15:1446725. doi: 10.3389/fphar.2024.1446725. eCollection 2024.
Arginine deprivation therapy (ADT) hinders glioma cells' access to nutrients by reducing peripheral blood arginine, showing great efficacy in various studies, which suggests it as a potentially promising treatment for glioma. The aim of this systematic review was to explore the mechanism of ADT for gliomas, the therapeutic effect based on existing research, and possible combination therapies.
We performed a systematic literature review of PubMed, ScienceDirect and Web of Science databases according to PRISMA guidelines, searching for articles on the efficacy of ADT in glioma.
We identified 17 studies among 786 search results, among which ADT therapy mainly based on Arginine free condition, Arginine Deiminase and Arginase, including three completed clinical trials. ADT therapy has shown promising results and , with its safety confirmed in clinical trials. In the early phase of treatment, glioblastoma (GBM) cells develop protective mechanisms of stress and autophagy, which eventually evolve into caspase dependent apoptosis or senescence, respectively. The immunosuppressive microenvironment is also altered by arginine depletion, such as the transformation of microglia into a pro-inflammatory phenotype and the activation of T-cells. Thus, ADT therapy demonstrates glioma-killing effect in the presence of a combination of mechanisms. In combination with various conventional therapies and investigational drugs such as radiotherapy, temozolomide (TMZ), cyclin-dependent kinase inhibitors (CDK) inhibitors and autophagy inducers, ADT therapy has been shown to be more effective. However, the phenomenon of drug resistance due to re-expression of ASS1 rather than stem cell remains to be investigated.
Despite the paucity of studies in the literature, the available data demonstrate the therapeutic potential of arginine deprivation therapy for glioma and encourage further research, especially the exploration of its combination therapies and the extrapolation of what we know about the effects and mechanisms of ADT from other tumors to glioma.
精氨酸剥夺疗法（ADT）通过减少外周血精氨酸来阻碍胶质瘤细胞获取营养，在各项研究中显示出巨大疗效，这表明它是一种潜在的有前景的胶质瘤治疗方法。本系统评价的目的是探讨ADT治疗胶质瘤的机制、基于现有研究的治疗效果以及可能的联合治疗方法。
我们根据PRISMA指南对PubMed、ScienceDirect和Web of Science数据库进行了系统的文献综述，搜索关于ADT治疗胶质瘤疗效的文章。
在786条搜索结果中，我们确定了17项研究，其中ADT治疗主要基于无精氨酸条件、精氨酸脱亚氨酶和精氨酸酶，包括三项完成的临床试验。ADT治疗已显示出有前景的结果，并且其安全性在临床试验中得到了证实。在治疗早期，胶质母细胞瘤（GBM）细胞会形成应激和自噬的保护机制，最终分别演变为半胱天冬酶依赖性凋亡或衰老。精氨酸耗竭也会改变免疫抑制微环境，例如小胶质细胞转变为促炎表型以及T细胞的激活。因此，ADT治疗在多种机制共同作用下显示出杀伤胶质瘤的效果。与各种传统疗法和研究性药物如放疗、替莫唑胺（TMZ）、细胞周期蛋白依赖性激酶抑制剂（CDK）抑制剂和自噬诱导剂联合使用时，ADT治疗已被证明更有效。然而，由于ASS1重新表达而非干细胞导致的耐药现象仍有待研究。
尽管文献中的研究较少，但现有数据证明了精氨酸剥夺疗法对胶质瘤的治疗潜力，并鼓励进一步研究，特别是探索其联合治疗方法，以及将我们对ADT在其他肿瘤中的作用和机制的了解外推到胶质瘤。
