Sorafenib-Inhibited Signaling: Emerging Evidence of RAF-Independent Pathways as Potential Therapeutic Targets in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide [Serag et al., 2007, Liovet et al., 2003, Yang et al., 2010]. More than 500,000 people are diagnosed with HCC every year, and it remains the leading cause of death among patients with hepatitis B virus (HBV), hepatitis C virus (HCV) and alcohol-induced liver cirrhosis. One of the main obstacles for treating HCC is late diagnosis of patients. Many unresectable HCC patients are treated with loco-regional therapies such as radiofrequency ablation and transarterial chemo‐ embolization (TACE), but the prognosis remains poor [Bruix et al., 2005]. A recent study in multiple clinical facilities in Japan reported that 5-year survival of patients treated with TACE was less than 30% [Takayasu et al., 2006]. Moreover, HCC is poorly responsive to chemother‐ apeutic drugs and radiotherapy [Arii et al., 2000, Kuwahara et al., 2009]; thus, effective therapeutic tools for HCC are long-awaited.