Regulation of Hepatocellular Carcinoma Epithelial-Mesenchymal Transition Mechanism and Targeted Therapeutic Approaches

Hepatocellular carcinoma (HCC) is a primary liver malignancy that accounts for the majority of liver cancer cases, with multiple risk factors including chronic hepatitis B and C infections, alcohol abuse, and non-alcoholic fatty liver disease (NAFLD). Despite advancements in diagnosis and treatment, the survival rate of patients with advanced HCC remains low, creating an urgent need for new therapeutic targets and strategies. One biological process crucial to HCC progression is the epithelial-mesenchymal transition (EMT). EMT is a process that enables epithelial cells to acquire mesenchymal properties, including motility and invasiveness, by losing their cell-cell adhesion. Various signaling pathways, including TGF-β, Wnt/β-catenin, and Notch, have been implicated in regulating EMT in HCC. To inhibit EMT, targeted therapeutic approaches have been developed, and preclinical studies suggest that the inhibition of the TGF-β, Wnt/β-catenin, and Notch signaling pathways is promising. TGF-β receptor inhibitors, Wnt/β-catenin pathway inhibitors, and gamma-secretase inhibitors have shown efficacy in preclinical studies by inhibiting EMT and reducing tumor growth in HCC models. However, further clinical studies are necessary to determine their effectiveness in human patients. In addition to these approaches, further research is needed to identify other novel therapeutic targets and develop new treatment strategies for HCC. This review emphasizes the critical role of EMT in HCC progression and highlights the potential of targeting the TGF-β, Wnt/β-catenin, and Notch signaling pathways to inhibit EMT and reduce tumor growth in HCC. Future studies and clinical trials are necessary to validate these therapeutic strategies and develop effective treatments for HCC.