Molecular targeted therapy for hepatocellular carcinoma in the current and potential next strategies

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and its incidence is still increasing. While the primary curative treatment for HCC is surgical resection, a major obstacle for the treatment of HCC is the high frequency of tumor recurrence even after curative resection. Effective palliative treatment is hindered by the evidence that HCC is frequently resistant to conventional chemotherapy and radiotherapy. Targeted therapy which specifically inhibits molecular abnormalities has emerged as a novel approach for the innovative and effective medical treatment of malignancies. In order to fulfill this promise there is an urgent need to identify the optimal targets for the treatment of HCC. A multi-kinase angiogenesis inhibitor, sorafenib, has been revealed as the first agent to show favorable overall survival in patients with advanced HCC. A new era of HCC treatment has arrived, but there has been limited improvement in survival benefits with the status quo. This review summarizes molecular targeted therapy for HCC, with a focus on angiogenesis, growth signaling, and mitosis, as well as a promising concept, "cancer stemness" for the current and potential next strategies of HCC treatment.

Monoclonal Antibody Targeting of the Cell Surface Molecule TM4SF5 Inhibits the Growth of Hepatocellular Carcinoma

“…HCC is also the most common type of liver cancer and is usually associated with prior hepatitis virus infection or liver cirrhosis. The primary treatment for HCC is surgical resection; however, the high frequency of recurrence and poor liver function following the removal of liver tissue are significant obstacles to recovery (3). Furthermore, HCC is frequently resistant to conventional chemotherapy and radiotherapy (4).…”

“…Furthermore, HCC is frequently resistant to conventional chemotherapy and radiotherapy (4). Therefore, understanding the signaling pathways involved in HCC development and developing targeted therapies is likely to be an important strategy for the effective treatment of HCC (3,5).…”

Decreased Blood Flow after Sorafenib Administration Is an Imaging Biomarker to Predict Overall Survival in Patients with Advanced Hepatocellular Carcinoma

“…Sorafenib inhibits Raf protein kinase and receptor tyrosine kinases, including platelet-derived growth factor receptor and vascular endothelial growth factor receptor, which is involved in the neovascularization of HCC. In addition, sorafenib also inhibits Flt-3 and c-KIT, which are both involved in neovascularization and cellular growth [31,32,33]. However, because both trials were assessed using the Response Evaluation Criteria in Solid Tumors 1.1 (RECIST1.1), altered arterial enhancement and its association with overall survival (OS) in sorafenib-treated patients has not been evaluated thus far [34].…”

Therapeutic effect of a TM4SF5-specific peptide vaccine against colon cancer in a mouse model

“…Therefore, understanding the main molecular signatures of cancers and screening proper targets of therapy are very important to treat cancers. Recently, molecular-targeted therapy involving tumor specific antigens or tumor-associated antigens has gained attention because these approaches are expected to have high efficacy and low side effects (15,16).…”