Dysregulated lipid metabolism in hepatocellular carcinoma: a review of molecular networks and therapeutic opportunities

BACKGROUND: Hepatocellular carcinoma (HCC), characterized by high incidence and mortality rates, is a major global health concern. Most patients are diagnosed at advanced stages, rendering surgical options unfeasible. Current treatments, including interventional therapy, chemotherapy, targeted therapy, and immunotherapy, yield limited success, underscoring the need for novel therapeutic targets. Lipid metabolism, a critical physiological process, has been intricately linked to HCC development and progression owing to its reprogramming in tumors and other associated cells within the tumor microenvironment (TME). AIM OF REVIEW: This review aims to summarize the research progress on lipid metabolism reprogramming in the context of HCC, integrate existing evidence that lipid metabolism drives HCC progression and immune dysregulation, clarify the underlying molecular regulatory mechanisms, identify potential therapeutic targets for improving HCC treatment efficacy, and outline strategies to address the associated therapeutic challenges. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review provides a comprehensive analysis of the research history and emerging trends regarding the role of lipid metabolism in HCC. We integrated key molecular networks involving lipid metabolic reprogramming in HCC cells and its associated TME. We also highlight significant overlaps between lipid metabolism-related genes and HCC progression loci, as well as syntenic relationships with other cancer types. These findings offer insights into the interplay between lipid metabolism, tumor development, and the immune response and suggest novel therapeutic targets to overcome current treatment limitations in patients with HCC.