Growth factors as therapeutic targets in HCC

Despite various effective local treatments for hepatocellular carcinoma (HCC), some patients do not meet the treatment criteria because of extrahepatic metastases or macroscopic vascular invasion at the time of their diagnosis. Furthermore, many patients treated with successful local treatments develop recurrences after treatment. Although these patients receive systemic treatment including chemotherapy, HCC is generally recognized as a chemo-resistant tumor. Recently, new molecular targets have been confirmed and various targeted agents are now being investigated for the treatment of HCC. Epidermal growth factor receptor (EGFR) is frequently expressed in human hepatoma cells, and EGF may be one of the mitogens that are needed for the growth of hepatoma cells. HCC is generally hypervascular, and vascular endothelial growth factor (VEGF) promotes HCC development and metastasis. Various inhibitors targeting EGFR and/or VEGF, VEGF receptor (VEGFR) have been developed as treatments of HCC. In phase-II studies of these growth factor inhibitors, the response rates are relatively low; however, high rates of disease control, enabling a good time to progression, have been achieved. Recently, a randomized phase III trial of sorafenib versus placebo conducted in patients with advanced HCC demonstrated the beneficial effects of this drug on the time-to-progression and overall survival of the patients, and the drug could become established as the standard chemotherapeutic agent for advanced HCC. Further clinical trials using biologic agents are warranted to prolong the survival in HCC patients.