Targeting amino acid metabolism in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains lethal due to its high refractoriness to standard treatment, which is contributed to by factors including adaptive metabolic reprogramming of HCC cells and pre-existing liver diseases that compromise liver function. Abnormal tumor vasculature creates a nutrient-deprived microenvironment, intensifying competition between HCC cells and immune cells and impairing antitumor immunity. Among the complex metabolic network, amino acid (AA) metabolism emerges as a critical player and an attractive therapeutic target. This review first examines how dysregulated AA metabolism supports HCC hallmarks, including metabolic reprogramming and immune evasion. We discuss the translational potential of therapies targeting AA metabolism in HCC, ranging from pharmacologic inhibition to dietary AA intervention, which can be further integrated with existing HCC treatments to improve clinical outcomes.