Glutamine Addiction: A New Therapeutic Target in Cancer

Glutamine Addiction: A New Therapeutic Target in Cancer

2010 August ; 35(8): 427–433. doi:10.1016/j.tibs.2010.05.003. | David R. Wise and Craig B. Thompson
The article discusses the role of glutamine in cancer cell metabolism and its potential as a therapeutic target. It highlights that while most cancers rely on aerobic glycolysis, they also exhibit a dependency on glutamine, which is a nonessential amino acid. Glutamine is not only a nitrogen donor for nucleotide and amino acid biosynthesis but also plays a crucial role in maintaining mitochondrial function and redox balance. Cancer cells are "glutamine-addicted," meaning they cannot survive without exogenous glutamine. This addiction is due to the high rate of glutamine uptake and its essential role in supporting protein synthesis and mitochondrial metabolism. The article explores how glutamine contributes to the activation of the mTORC1 signaling pathway, which is critical for cell growth and protein translation. It also discusses the role of glutamine in mitochondrial metabolism, where it serves as a substrate for the TCA cycle and is essential for maintaining mitochondrial membrane potential and the production of NADPH. Additionally, the article examines the regulation of glutamine metabolism by oncogenic proteins such as c-MYC, which enhances glutamine uptake and metabolism to support cancer cell growth. The article also reviews the development of therapeutic strategies targeting glutamine addiction, including the use of glutamine analogs and inhibitors of glutamine transporters. These approaches aim to disrupt the metabolic pathways that cancer cells rely on for survival. The potential of targeting glutamine metabolism for cancer therapy is discussed, with a focus on the importance of glutamine in cancer cell viability and the challenges in developing effective treatments that specifically target this pathway without affecting normal tissues. The review concludes that glutamine metabolism is a promising therapeutic target, and further research is needed to develop safe and effective therapies that exploit this vulnerability in cancer cells.The article discusses the role of glutamine in cancer cell metabolism and its potential as a therapeutic target. It highlights that while most cancers rely on aerobic glycolysis, they also exhibit a dependency on glutamine, which is a nonessential amino acid. Glutamine is not only a nitrogen donor for nucleotide and amino acid biosynthesis but also plays a crucial role in maintaining mitochondrial function and redox balance. Cancer cells are "glutamine-addicted," meaning they cannot survive without exogenous glutamine. This addiction is due to the high rate of glutamine uptake and its essential role in supporting protein synthesis and mitochondrial metabolism. The article explores how glutamine contributes to the activation of the mTORC1 signaling pathway, which is critical for cell growth and protein translation. It also discusses the role of glutamine in mitochondrial metabolism, where it serves as a substrate for the TCA cycle and is essential for maintaining mitochondrial membrane potential and the production of NADPH. Additionally, the article examines the regulation of glutamine metabolism by oncogenic proteins such as c-MYC, which enhances glutamine uptake and metabolism to support cancer cell growth. The article also reviews the development of therapeutic strategies targeting glutamine addiction, including the use of glutamine analogs and inhibitors of glutamine transporters. These approaches aim to disrupt the metabolic pathways that cancer cells rely on for survival. The potential of targeting glutamine metabolism for cancer therapy is discussed, with a focus on the importance of glutamine in cancer cell viability and the challenges in developing effective treatments that specifically target this pathway without affecting normal tissues. The review concludes that glutamine metabolism is a promising therapeutic target, and further research is needed to develop safe and effective therapies that exploit this vulnerability in cancer cells.
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