Targeting glutamine metabolism as a therapeutic strategy for cancer

• Published in: Experimental & molecular medicine Vol. 55; no. 4; pp. 706 - 715
• Main Authors: Jin, Jonghwa, Byun, Jun-Kyu, Choi, Yeon-Kyung, Park, Keun-Gyu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2023; Springer Nature B.V; Nature Publishing Group; 생화학분자생물학회
• Subjects: 13/51; 38; 631/67/2327; 692/699/67/2327; 82/1; Amino acids; Amino Acids - metabolism; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer therapies; Carbon sources; Cell proliferation; Citric Acid Cycle; Clinical trials; Glutamine; Glutamine - metabolism; Homeostasis; Humans; Lipid metabolism; Medical Biochemistry; Metabolism; Metabolites; Molecular Medicine; Neoplasms - metabolism; Oxidation-Reduction; Review; Review Article; Stem Cells; Tricarboxylic acid cycle; Tumor Microenvironment; Tumors; 생화학
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/s12276-023-00971-9

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. Cancer: Targeting glutamine metabolism as potential treatment Further insights into metabolic reprogramming by cancer cells are needed to determine if targeting glutamine metabolism could be a useful therapeutic approach. Cancer cells rely on the amino acid glutamine for growth and proliferation. Glutamine is a key nitrogen source and enables the cells to synthesize critical molecules including lipids and metabolites. Blocking glutamine metabolism may be useful in treating cancers, but care must be taken due to glutamine’s multiple roles. Keun-Gyu Park and Yeon-Kyung Choi at Kyungpook National University in Daegu, South Korea, and co-workers reviewed current knowledge of the steps involved in glutamine metabolism to identify opportunities for intervention. Cancers can evade glutamine metabolism inhibition by manipulating the tumor microenvironment and finding alternative ways to source nutrients. Drug trials have targeted aspects of glutamine metabolism with mixed success, inhibition of glutamine transporters showing promise.