Targeted Therapy for Hepatocellular Carcinoma: What`s New?

Hepatocellular carcinoma (HCC), one of the most frequent neoplasms worldwide, causes more than 700,000 deaths per year, and is the third cause of cancer-related mortality. 1-3 HCC occurs after years of damage to hepatocytes with inflammatory conditions due to Hepa - titis B Virus (HBV) or Hepatitis C Virus (HCV) infection resulting in chronic hepatitis and/ or cirrhosis. The disease incidence is decreasing due to Hepatitis B Virus (HBV) vaccination, whereas rates are steadily increasing in Europe and United States possibly due to increased obesity and Hepatitis C Virus (HCV) infection. 3 The latest antiviral drug, Sofosbuvir (Sovaldi, Gilead), has achieved notable success in clinical trials and approved against HCV and gives great hopes for treatment and hopefully preventing HCV induced liver cancer. Unfortunately, other risk factors like alcohol abuse, fungal toxins, obesity, and poor diet are also associated with HCC and will not be easily wiped out anytime soon. If diagnosed early, HCC can be cured with surgery or liver transplant. However, most HCC cases can only be diagnosed at advanced stages, and are accompanied with chronic liver disease such as hepatitis and fatty liver disease. Sorafenib, the only approved multi-kinase inhibitor, is the current first line therapy for the advanced HCC and can only lead to survival benefit of 2-3 months. Sorafenib inhibits the growth of blood vessel formation and the cancer cells by targeting key kinases like RAF-1, B-RAF, VEGFR and PDGFR. 4 Since the approval of Sorafenib, drug companies have spent tremendous effort for testing variety of molecular thera- pies targeting angiogenesis to oncogenic signaling pathways many of which still under clinical evaluation. Unfortunately, none of these drugs could exhibit superior efficacy to Sorafenib. The failure of these inhibitors can be explained by their lack of efficacy, toxicity and coexisting genetic and epigenetic alterations. 2 Thus, more radical approaches are required to treat HCC. Several clinical trials are currently testing the safety and efficacy of multi-tyrosine kinase in - hibitors and other targeted therapy agents alone or in combination with Sorafenib in advanced HCC. Here, we summarize the current state and emerging novel targeted therapies as well as ongoing clinical trials for the treatment of HCC.