Glutamine Metabolism and Prostate Cancer.

Simple Summary: Glutamine (Gln) plays a critical role in the development and progression of prostate cancer (PCa). Non-malignant prostate cells are not addicted to Gln, but PCa cells become Gln-dependent due to the low levels of the Gln-producing enzyme glutamine synthetase. Gln metabolism in PCa is controlled by oncogenes such as MYC, AR, and mTOR, which contribute to therapy resistance and more aggressive forms of the disease. Studies have shown that depriving PCa cells of Gln can inhibit their growth and survival and make them more sensitive to radiotherapy. Targeting Gln metabolism is, therefore, a promising approach for PCa treatment. Clinical trials are currently testing the safety and efficacy of drugs that inhibit Gln metabolism in combination with other therapies for different types of cancer, including PCa. Understanding of how tumor cells metabolically interact with their environment may help improve these treatments and patient outcomes. In this review, we present the latest advances in Gln research in PCa and insights into the current clinical trials. Glutamine (Gln) is a non-essential amino acid that is involved in the development and progression of several malignancies, including prostate cancer (PCa). While Gln is non-essential for non-malignant prostate epithelial cells, PCa cells become highly dependent on an exogenous source of Gln. The Gln metabolism in PCa is tightly controlled by well-described oncogenes such as MYC, AR, and mTOR. These oncogenes contribute to therapy resistance and progression to the aggressive castration-resistant PCa. Inhibition of Gln catabolism impedes PCa growth, survival, and tumor-initiating potential while sensitizing the cells to radiotherapy. Therefore, given its significant role in tumor growth, targeting Gln metabolism is a promising approach for developing new therapeutic strategies. Ongoing clinical trials evaluate the safety and efficacy of Gln catabolism inhibitors in combination with conventional and targeted therapies in patients with various solid tumors, including PCa. Further understanding of how PCa cells metabolically interact with their microenvironment will facilitate the clinical translation of Gln inhibitors and help improve therapeutic outcomes. This review focuses on the role of Gln in PCa progression and therapy resistance and provides insights into current clinical trials. [ABSTRACT FROM AUTHOR]