New molecular targets for hepatocellular carcinoma: The ErbB1 signaling system

Abstract

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths. This malignancy is often diagnosed at an advanced state, when most potentially curative therapies are of limited efficacy. In addition, HCC is a type of tumor highly resistant to available chemotherapeutic agents, which leaves HCC patients with no effective therapeutic options and a poor prognosis. From a molecular perspective, HCC is a heterogeneous type of tumor. However, in most cases, HCC emerges on a background of persistent liver injury, inflammation and hepatocellular proliferation, which is characteristic of chronic hepatitis and cirrhosis. Recent studies have revealed that dysregulation of a limited number of growth and survival-related pathways can play a key role in HCC development. The epidermal growth factor receptor (ErbB1) can be bound and activated by a broad family of ligands, and can also engage in extensive cross talk with other signaling pathways. This system is considered as an important defense mechanism for the liver during acute tissue injury; however, accumulating evidences suggest that its chronic stimulation can participate in the neoplastic conversion of the liver. Agents that target the ErbB1 receptor have shown antineoplastic activity in other types of tumors, but their efficacy either alone or in combination with other compounds has just started to be tested in experimental and human HCC. Here, we review the evidences that support the involvement of the ErbB1 in HCC development and that provide a rationale for ErbB1 targeting in HCC prevention and treatment. © 2007 Blackwell Munksgaard.