Targeting c-Met as a promising strategy for the treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a severe condition that is found worldwide. Liver transplantation, surgical resection, and local-regional therapy such as transarterial chemoembolization have made great progress and play a dominant role in HCC management. However, the high frequency of tumor recurrence and/or metastasis after those treatments acquires systematic drug intervention. The approval of sorafenib, an agent that targets receptor tyrosine kinases (RTKs), as the first effective drug for systemic treatment of HCC represents a milestone in treatment of this disease. As a typical member of the RTK family, c-Met represents an intriguing target for cancer therapy. However, the role of the c-Met signal transduction pathway is less unambiguous in HCC pathology, giving rise to concerns about the feasibility of utilizing c-Met targeting approaches for HCC treatment. Recently, studies on des-gamma-carboxy prothrombin, an abnormal cytokine secreted by HCC cells, by the current authors and other researchers have highlighted the critical role of c-Met signaling in HCC progression. This review takes a second look at the c-Met signal transduction pathway and discusses the possibility of targeting c-Met as a therapeutic strategy for HCC treatment. (C) 2011 Elsevier Ltd. All rights reserved.