The Developing Role of Sorafenib in the Management of Hepatocellular Carcinoma

Despite the significant therapeutic armamentarium existing for the treatment of hepatocellular carcinoma (HCC), there is a spectacular lack of chemotherapeutic agents. A noticeable exception is sorafenib, a multikinase inhibitor against Raf kinase. Despite the attractiveness of the tumor antiangiogenic mechanism of sorafenib, it has only gained acceptance in clinical use in cases of advanced HCC, as it has been shown to increase survival by approximately 3 months. This comes at a significant financial cost for the health care system, in addition to the potential adverse events for the patient.

This chapter will explore the mechanism of action for sorafenib, including the potential of antiangiogenic agents in the management of HCC. Additionally, the current experience with its use will be analyzed, as well as the problems encountered with the complications of the medication. More importantly, the ultimate goal of the paper is to further explore the proposed use of sorafenib in different stages of the treatment continuum, as it may hold more promise than currently thought. Specifically, there have been thoughts and attempts to use the medication prior to a liver transplant, or following a liver transplant or a hepatectomy, in an attempt to avoid recurrence. Several drugs are under investigation in clinical trials after the failure of sorafenib, or in combination with sorafenib. Looking into these questions may help identify its proper place in the management of HCC, as well as its true potential.

Keywords: Advanced stage, complication, hepatocellular carcinoma, hepatic resection, liver failure, multikinase inhibitor, orthotopic liver transplantation, rapamycin, signaling pathways, sorafenib, targeted therapy, treatment, tumor angiogenesis.