Volume 11,Issue 3
Molecular Subtyping of Hepatocellular Carcinoma and Precision Systematic Treatment Strategies
Hepatocellular carcinoma (HCC) is a highly heterogeneous malignant tumor determined by multiple molecular driver events and tumor microenvironment remodeling. Multidisciplinary integrated studies have systematically revealed that HCC can be classified into several functional subtypes with internal consistency in multi-level molecular characteristics but significant differences among subtypes, including Wnt/β-catenin activated type, proliferative/chromosomal instability type, metabolic/hepatocyte-like type, and immune microenvironment-dominant type. These subtypes exhibit fundamental differences in signaling pathway dependence, immune ecological architecture, and therapeutic sensitivity, directly determining the efficacy of targeted therapy and immunotherapy. Current systemic therapies still face significant challenges in patient selection and resistance control, highlighting the necessity of precision treatment based on molecular subtyping. This review summarizes the biological basis of major molecular subtypes of HCC, focuses on subtype-guided strategies for immunotherapy combination, targeted therapy combination, and metabolic intervention, and emphasizes the potential value of dynamic subtyping and resistance monitoring in precision systemic therapy.
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