Mechanistic Insights into Resistance to Conversion Therapy in Hepatocellular Carcinoma
NIU Yi, LI Binkui*, YUAN Yunfei*
Primary liver cancer is one of the most common malignancies in China. Due to its atypical early symptoms, the majority of patients are diagnosed at an intermediate or advanced stage, resulting in unresectable disease and poor survival. Conversion therapy for HCC aims to downstage initially unresectable tumors to resectable disease through interventional therapy, targeted therapy, and immunotherapy, thereby offering a chance for cure and improving survival. However, there are still many patients developed primary or acquired resistance to treatment, which limits the efficacy of conversion therapy. This review focuses on the molecular mechanisms driving resistance to conversion therapy in HCC, including aberrant signaling pathways, tumor microenvironment dynamics, cancer stem cell characteristics, as well as genetic and epigenetic alterations. Further investigation of resistance mechanisms is critical for identifying patient subgroups most likely to benefit from conversion therapy, developing tailed therapeutic strategies, and enhancing the overall therapeutic efficacy in HCC.
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