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利用癌症的阿喀琉斯之踵:破坏谷氨酰胺代谢以实现有效的癌症治疗。

Exploiting the Achilles' heel of cancer: disrupting glutamine metabolism for effective cancer treatment.

作者信息

Fan Yuxin, Xue Han, Li Zhimin, Huo Mingge, Gao Hongxia, Guan Xingang

机构信息

Department of Clinical Laboratory Diagnostics, School of Medical Technology, Beihua University, Jilin City, China.

Department of Basic Medicine, Medical School, Taizhou University, Taizhou, Zhejiang Province, China.

出版信息

Front Pharmacol. 2024 Mar 6;15:1345522. doi: 10.3389/fphar.2024.1345522. eCollection 2024.

Abstract

Cancer cells have adapted to rapid tumor growth and evade immune attack by reprogramming their metabolic pathways. Glutamine is an important nitrogen resource for synthesizing amino acids and nucleotides and an important carbon source in the tricarboxylic acid (TCA) cycle and lipid biosynthesis pathway. In this review, we summarize the significant role of glutamine metabolism in tumor development and highlight the vulnerabilities of targeting glutamine metabolism for effective therapy. In particular, we review the reported drugs targeting glutaminase and glutamine uptake for efficient cancer treatment. Moreover, we discuss the current clinical test about targeting glutamine metabolism and the prospective direction of drug development.

摘要

癌细胞通过重新编程其代谢途径,适应了肿瘤的快速生长并逃避免疫攻击。谷氨酰胺是合成氨基酸和核苷酸的重要氮源,也是三羧酸(TCA)循环和脂质生物合成途径中的重要碳源。在本综述中,我们总结了谷氨酰胺代谢在肿瘤发展中的重要作用,并强调了针对谷氨酰胺代谢进行有效治疗的薄弱环节。特别是,我们综述了报道的针对谷氨酰胺酶和谷氨酰胺摄取以实现高效癌症治疗的药物。此外,我们讨论了目前针对谷氨酰胺代谢的临床试验以及药物开发的未来方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69a7/10952006/bf7c6af94e8b/fphar-15-1345522-g001.jpg

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