Molecular pathogenesis and systemic therapies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) remains one of the most prevalent and deadliest cancers. The poor outcome associated with HCC is dramatically changing due to the advent of effective systemic therapies. Here we discuss the molecular pathogenesis of HCC, molecular classes and determinants of heterogeneity. In addition, effective single-agent and combination systemic therapies involving immunotherapies as standard of care are analyzed. Finally, we propose a flowchart of sequential therapies, explore mechanisms of resistance and address the need for predictive biomarkers. Llovet and colleagues review recent advances in hepatocellular carcinoma therapy and the clinical workflows for the selection and monitoring of patients undergoing systemic therapies and immunotherapy.