Systemic therapy in hepatocellular carcinoma

Abstract

Many potential systemic therapies are being investigated for the treatment of hepatocellular carcinoma (HCC). The incidence of this malignancy is rising sharply and the vast majority of patients present at advanced stages. Although the earlier dismal results with cytotoxic chemotherapies made way for the development of locoregional therapies that provided improved overall survival, truly personalized therapy will require the selection of phenotypically similar stages of disease and populations, an understanding of the complex molecular and genetic pathways leading to HCC, and a keen understanding of the pathobiology of cirrhosis. Only then will we understand how to offer a particular patient at a specific stage of disease the appropriate therapy to truly prolong survival.

Fig. 1

Summary of converging molecular pathways in HCC inhibited by targeted agents. Antibodies listed in italics and small molecular inhibitors in shaded rectangles. EGFR, epidermal growth factor receptor; PDGFR, platelet-derived growth factor receptor; VEGFR, vascular endothelial growth factor receptor; FGFR, fibroblast growth factor receptor; PDK, phosphate-dependent kinase; PTEN, phosphatase and tensin homolog deleted in chromosomes 10; mTOR, mammalian target of rapamycin; MEK, mitogen-activated protein kinase kinase; ERK, extracellular related kinase.