Systemic therapies in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common and lethal malignant tumors worldwide in the human population. Due to late diagnosis and/or advanced underlying liver cirrhosis, only limited treatment options with marginal clinical benefit are available in up to 70% of patients. During the last decades, no effective conventional cytotoxic systemic therapy was available contributing to the dismal prognosis in patients with advanced disease. However, a better knowledge of molecular hepatocarcinogenesis provides today the opportunity for targeted therapy. Positive data from the pivotal phase III SHARP trial assessing the efficacy and safety of the multikinase inhibitor sorafenib broadened the horizon for patients with advanced disease. After years of therapeutic nihilism, sorafenib was the first agent to demonstrate a statistically significant improvement in overall survival for patients with advanced HCC. This article reviews the historical perspective of systemic therapy in HCC and provides a brief overview of molecular hepatocarcinogenesis and potential targets in HCC. Most promising molecular targeted agents tested within clinical trials in advanced HCC are summarized, with a special attention to sorafenib, sunitinib, bevacizumab, and erlotinib.