Ribonucleotide Reductase Subunit M2 Can Be New Molecular Target and Prognostic Biomarker of Hepatocellular Carcinoma

After approval of imatinib for treatment of chronic myeloid leukemia, molecular-targeted therapies make change of the management strategies against cancers. Many target molecules have been revealed in several cancers such as lung cancer, breast cancer, colorectal cancer, and hematopoietic tumor. Representative molecular-targeted agents are trastuzumab for breast cancer, imatinib and rituximab for hematopoietic tumors, and gefitinib and erlotinib for lung cancer. These molecular-targeted agents improved patient’s survival and life quality. Hepatocellular carcinoma (HCC) is one of the popular cancers in the world. The prognosis is still poor even though we have tried to detect it at early stage and treat it properly with numerous treatment modalities such as transarterial chemoembolization (TACE), radiofrequency ablation (RFA), systemic cytotoxic chemotherapy, surgical resection and liver transplantation. Now, we have only one approved molecular-targeted agent against advanced HCC with limited efficacy, which is sorafenib as an inhibitor of tyrosine kinases such as the vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor (PDGFR). Unfortunately, the carcinogenesis pathway of HCC is not clear compared to other cancers. Several targets such as VEGFR, PDGFR, epidermal growth factor receptor, fibroblast growth factor receptor, and mammalian target of rapamycin (mTOR) were investigated recently and several moleculartargeted agents such as brivanib, sunitinib, linifanib erlotinib and everolimus were clinically studied but, the results were disappointing. Some signaling pathways including growth factor pathway, Jak/Stat pathway, Akt/mTOR pathway, Hedgehog pathway, Wnt/β-catenin pathway can be molecular targets for treatment of HCC. Although great efforts have been made for