Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, South Korea.
BK21 FOUR Community-based Intelligent Novel Drug Discovery Education Unit, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu, 41566, Korea.
Exp Mol Med. 2023 Apr;55(4):706-715. doi: 10.1038/s12276-023-00971-9. Epub 2023 Apr 3.
Proliferating cancer cells rely largely on glutamine for survival and proliferation. Glutamine serves as a carbon source for the synthesis of lipids and metabolites via the TCA cycle, as well as a source of nitrogen for amino acid and nucleotide synthesis. To date, many studies have explored the role of glutamine metabolism in cancer, thereby providing a scientific rationale for targeting glutamine metabolism for cancer treatment. In this review, we summarize the mechanism(s) involved at each step of glutamine metabolism, from glutamine transporters to redox homeostasis, and highlight areas that can be exploited for clinical cancer treatment. Furthermore, we discuss the mechanisms underlying cancer cell resistance to agents that target glutamine metabolism, as well as strategies for overcoming these mechanisms. Finally, we discuss the effects of glutamine blockade on the tumor microenvironment and explore strategies to maximize the utility of glutamine blockers as a cancer treatment.
增殖的癌细胞在很大程度上依赖于谷氨酰胺来生存和增殖。谷氨酰胺可作为 TCA 循环中脂质和代谢物合成的碳源，以及氨基酸和核苷酸合成的氮源。迄今为止，许多研究已经探讨了谷氨酰胺代谢在癌症中的作用，从而为针对谷氨酰胺代谢治疗癌症提供了科学依据。在这篇综述中，我们总结了谷氨酰胺代谢过程中每个步骤涉及的机制，从谷氨酰胺转运蛋白到氧化还原平衡，并强调了可以用于临床癌症治疗的领域。此外，我们讨论了癌细胞对靶向谷氨酰胺代谢的药物产生耐药性的机制，以及克服这些机制的策略。最后，我们讨论了谷氨酰胺阻断对肿瘤微环境的影响，并探讨了最大限度地利用谷氨酰胺阻断剂作为癌症治疗的策略。
