Hepatocellular carcinoma (HCC): the most promising therapeutic targets in the preclinical arena based on tumor biology characteristics.

INTRODUCTION: : Hepatocellular carcinoma (HCC) is a malignant liver tumor characterized by high molecular heterogeneity, which has hampered the development of effective targeted therapies severely. Recent experimental data have unraveled novel promising targets for HCC treatment. AREAS COVERED: : Eligible articles were retrieved from PubMed and Web of Science databases up to July 2021. This review summarizes the established targeted therapies for advanced HCC, focusing on the strategies to overcome drug resistance and the search for combinational treatments. In addition, conventional biomarkers holding the promises for HCC treatments and novel therapeutic targets from the research field are discussed. EXPERT OPINION: : HCC is a molecularly complex disease, with several and distinct pathways playing critical roles in different tumor subtypes. Experimental models recapitulating the features of each tumor subset would be highly beneficial to design novel and more effective therapies against this disease. Furthermore, a deeper understanding of combinatorial drug synergism and the role of the tumor microenvironment in HCC will lead to improved therapeutic outcomes.