Amino acid transporters in hepatocellular carcinoma: Gatekeepers of metabolic reprogramming

Hepatocellular carcinoma (HCC), an aggressive cancer predisposed to notable metabolic alterations, including an imbalance in amino acid transporters, remains a global concern. Amino acid transporters such as proton-assisted amino acid transporter (PAT), sodium-coupled neutral amino acid transporter (SNAT), cysteine/glutamate transporter (xCT), L-type amino acid transporter (LAT1), and Alanine-serine-cysteine transporter 2 (ASCT2). The tumour microenvironment (TME), cellular signalling pathways, tumour survival, and proliferation all depend heavily on these transporters. Current investigation of these transporters is fundamental in regulating the imbalance. Emerging therapeutics, including RNA-based therapeutics, small-molecule inhibitors and combinational treatment strategies with dietary intervention in metabolic reprogramming and oncological signalling are also discussed. The emergence of problems like tumour heterogeneity, transporter redundancy, off-target toxicity, and resistance mechanisms is substantial, even with available treatment options. A thorough understanding of amino acid transporters in HCC, including their emerging functions, might reveal metabolic vulnerabilities that could inform creative treatments for better outcomes.