Implication of hepatocyte dedifferentiation in pathogenesis and treatment of hepatocellular carcinoma

Liver cancer is the fifth most common malignancy worldwide and the third most common cause of cancer-related death. Five hundred million individuals are infected by hepatitis B or C virus. Of these cases, some will progress to liver failure and cancer. Systemic treatments against liver cancer show poor efficacy mainly because of high resistance and poor response to therapeutics and high degree of tumor heterogeneity. Although progress has been made in combinational treatment of liver cancer, no effective disease-modifying therapies for hepatocellular carcinoma (HCC) have been developed to date. A comprehensive understanding of HCC pathogenesis will enable identification of biomarkers and therapeutic targets and provide insights into mechanism-based strategies for HCC treatment. However, the identification of cellular origins of liver cancer remains a challenging issue. This review focuses on HCC heterogeneity that escapes current treatment strategies and causes disease recurrence to provide a better understanding for the biology of liver cancer.