Molecular targeted therapies in hepatocellular carcinoma: From pre-clinical models to clinical trials

Hepatocellular carcinoma (HCC) is one of the world’s most common and deadly cancers. Less than one-third of patients can currently benefit from potentially curative therapies in the West [1]. However, a new era has dawned in oncology with novel and promising drugs emerging in parallel with a better understanding of the pathogenesis of cancer [2]. The advent of sorafenib – a multikinase inhibitor – as an effective therapy in advanced HCC has enhanced the interest in testing new molecular therapies in experimental and clinical studies [3]. Integrative genomic studies in human HCC samples have begun to identify subgroups of patients with characteristic molecular features such as mutations, gene expression profiles and chromosomal aberrations [4,5]. These studies have underlined the fact that a number of molecular pathways are disrupted in almost all tumors, involving critical functions for the progression or dissemination of the disease. Such is the case of three main cellular functions: (1) Activation of pro-angiogenic signals mediated by VEGF, PDGER,