Decoding amino acid metabolism in hepatocellular carcinoma: critical nodes and novel therapeutic strategy

Amino acid metabolic reprogramming is one of the crucial features of metabolic remodeling in HCC. Accumulating evidence indicates that specific amino acid metabolisms play essential roles in promoting HCC cell proliferation and the development of drug resistance. Notably, recent studies have demonstrated that regulating the intake of particular amino acids can significantly enhance the efficacy of clinical interventions for HCC, suggesting that amino acid metabolism is emerging as a promising target for therapeutic strategies. However, some key scientific questions remain unresolved, including the intrinsic relationships between the metabolism of different amino acids and their precise roles in HCC progression. In this article, we systematically review the molecular and cellular mechanisms underlying amino acid metabolic reprogramming, focusing on glutamine, arginine, and tryptophan, and explore their potential interconnections in HCC. Additionally, we update recent advances in amino acid metabolism and clinical management of HCC. Importantly, we discuss key challenges that must be addressed in future research, aiming to provide a theoretical foundation for developing novel clinical interventions targeting amino acid metabolic reprogramming in HCC.