Research progress and therapeutic strategies in hepatocellular carcinoma metabolic reprogramming

BACKGROUND: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, with therapeutic resistance posing a significant clinical challenge. Metabolic reprogramming, a hallmark of cancer, enables tumor cells to alter metabolic pathways to meet their increased energy and biosynthetic demands, playing a critical role in HCC initiation, progression, and drug resistance. AIM OF REVIEW: This review aims to elucidate the mechanisms underlying metabolic alterations in HCC, including fatty acid, protein, and amino acid metabolism, and to explore their implications in tumor progression and therapeutic resistance. Additionally, it highlights emerging therapeutic strategies targeting key enzymes in metabolic pathways for HCC. KEY SCIENTIFIC CONCEPTS OF REVIEW: Metabolism reprogramming is closely associated with HCC proliferation and metastasis, while the interplay between metabolic pathways further drives disease progression. Targeting key metabolic enzymes and pathways through combination therapies and novel drug development shows promising clinical potential. This review provides a comprehensive analysis of metabolic reprogramming in HCC and underscores the importance of understanding these mechanisms to develop more effective therapeutic interventions.