Department of Stem Cell and Regenerative Medicine, Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
International Joint Research Center for Precision Biotherapy, Ministry of Science and Technology, Chongqing, China.
J Enzyme Inhib Med Chem. 2024 Dec;39(1):2367129. doi: 10.1080/14756366.2024.2367129. Epub 2024 Jul 25.
Metabolic abnormalities are an important feature of tumours. The glutamine-arginine-proline axis is an important node of cancer metabolism and plays a major role in amino acid metabolism. This axis also acts as a scaffold for the synthesis of other nonessential amino acids and essential metabolites. In this paper, we briefly review (1) the glutamine addiction exhibited by tumour cells with accelerated glutamine transport and metabolism; (2) the methods regulating extracellular glutamine entry, intracellular glutamine synthesis and the fate of intracellular glutamine; (3) the glutamine, proline and arginine metabolic pathways and their interaction; and (4) the research progress in tumour therapy targeting the glutamine-arginine-proline metabolic system, with a focus on summarising the therapeutic research progress of strategies targeting of one of the key enzymes of this metabolic system, P5CS (ALDH18A1). This review provides a new basis for treatments targeting the metabolic characteristics of tumours.
代谢异常是肿瘤的一个重要特征。谷氨酰胺-精氨酸-脯氨酸轴是癌症代谢的一个重要节点，在氨基酸代谢中起着主要作用。该轴还充当合成其他非必需氨基酸和必需代谢物的支架。在本文中，我们简要回顾了（1）具有加速谷氨酰胺转运和代谢的肿瘤细胞表现出的谷氨酰胺成瘾；（2）调节细胞外谷氨酰胺进入、细胞内谷氨酰胺合成和细胞内谷氨酰胺命运的方法；（3）谷氨酰胺、脯氨酸和精氨酸代谢途径及其相互作用；（4）针对谷氨酰胺-精氨酸-脯氨酸代谢系统的肿瘤治疗的研究进展，重点总结了针对该代谢系统关键酶之一 P5CS（ALDH18A1）的靶向治疗策略的治疗研究进展。本综述为针对肿瘤代谢特征的治疗提供了新的依据。
