**1. Introduction**

36 Liver Tumors

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Hepatocellular carcinoma (HCC) is the sixth most common type of cancer in the world, with approximately 630,000 new cases each year (Alves et al., 2011). It is also the third most common cause of cancer related mortality (Parkin et al., 2005). Moreover, the incidence of HCC has risen in many countries over the past decade. The greatest risk factor associated with the development of HCC is hepatitis B and C virus infection. Hepatitis infection is believed to increase the risk of developing HCC by 20 fold and is the major etiological factor in more than 80% of HCC cases (Anzola, 2004). Other main risk factors include excessive alcohol consumption, non alcoholic steatohepatitis, exposure to environmental toxins such as aflatoxin B, hemochromatosis, cirrhosis, diabetes and obesity (El-Serag et al., 2006; Hassan et al., 2010; Whittaker et al., 2010).

The standard treatments for early stage HCC, such as surgical resection and liver transplantation, can cure certain population of patients. However, due to the asymptomatic nature of early HCC and lack of effective screening strategies, 80% of patients present with advanced HCC at the time of diagnosis (Thomas and Abbruzzese, 2005). These patients have rather limited treatment options which are mainly palliative. If the patient has developed HCC that is surgical unresectable, systemic treatments are commonly used. However, conventional chemotherapy with cytotoxic agents is not very effective in changing the progress of the tumor growth. Consequently, the mortality rate for advanced stage HCC is quite high, and 5 year survival rate for patients with HCC is only 7% (Bosch et al., 2004; Whittaker et al., 2010). There is clearly an urgent medical need to develop new effective and well-tolerated HCC treatment options.

In recent decades, tremendous progress has been made toward better understanding the molecular mechanisms of oncogenic processes. Many cell signaling pathways involved in tumor pathogenesis have been identified, leading to the identification of new molecular targets for therapeutic development. Unlike conventional chemotherapy which utilizes broad spectrum cytotoxic agents, targeted therapy acts directly and specifically on the components that regulate tumorigenesis. This strategy has shown clinical benefits in various tumor types, such as breast, colorectal and lung cancers (Ansari et al., 2009; Slamon et al., 2001; Takahashi and Nishioka, 2011). Several major cellular signaling pathways have been implicated in HCC, and below we will review those pathways and discuss the potential to target the molecular components within those signaling pathways.
