The arginine metabolism and its deprivation in cancer therapy

Abstract

Arginine deprivation has emerged as a promising therapeutic strategy in cancer treatment due to the auxotrophy of certain tumors. Many cancers, such as pancreatic, colorectal, and hepatocellular carcinoma, exhibit downregulated argininosuccinate synthetase, making them reliant on external arginine sources. This dependency allows targeted therapies that deplete arginine, inhibiting tumor growth while sparing normal cells. Arginine is crucial for various cellular processes, including protein synthesis and immune function. Its deprivation affects both tumor metabolism and immune responses, potentially enhancing cancer therapy. Studies have explored using enzymes like arginine deiminase and arginase, often modified for increased stability and reduced immunogenicity, to effectively lower arginine levels in the tumor microenvironment. These approaches show promise, particularly in tumors with low argininosuccinate synthetase expression. However, the impact on immune cells and the potential for resistance highlight the need for further research. Combining arginine deprivation with other treatments might improve outcomes, offering a novel approach to combat arginine-dependent cancers.