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Abstract
Hepatocellular carcinoma (HCC) is a highly malignant tumor that has limited treatment options in its advanced state. The efficacy of current anti-cancer chemotherapy in advanced HCC has not been satisfactory, and the management of HCC remains a major challenge for physicians. However, recent advancement in our understanding of the molecular mechanisms underlying carcinogenesis has provided novel targets in key signaling pathways for tumor development. Recently, Sorafenib (Nexavar), a multi-kinase inhibitor targeting membrane receptors involved in angiogenic and mitogenic intra-cellular signaling including Raf, vascular endothelial growth factor receptor (VEGFR), and platelet-derived growth factor receptors (PDGFR), has been approved worldwide as a new target agent for HCC, and subsequent clinical trials of newly developed molecular target agents such as Brivanib and Everolimus are being conducted globally. In the near future, continued research will lead to the identification of additional molecular targets in HCC and lead to treatments with enhanced efficacy and improved tolerability.
Figures and Tables
Fig. 1
The etiologic factors and pathogenesis of hepatocellular carcinoma. HBV, hepatitis B virus; HCV, hepatitis C virus; NASH, nonalcoholic steatohepatitis; AFB1, aflatoxin B1; p53, tumor suppressor gene p53.
Fig. 2
Signaling pathways in hepatocarcinogenesis. Wnt/Hedgehog pathway, growth factor pathway, survival factor pathway, Akt/mTOR pathway, and Jak/stat pathway are involved in the hepatocarcinogenesis, and can be targeted for HCC therapy. DSH, Dishevelled; GBP,GSK3B binding protein; GSK3B, glycogen synthase kinase 3-beta; APC, adenomatous polyposis coli; PTCH1, PATCHED1 membrane protein; SMOH, Smoothened; SU, suppressor-of-fused; COS-2, Drosophila Costal2; FU, Fused; PI3K, phosphoinositide 3-kinase; GLI, glioblastoma; RTK, receptor tyrosine kinase; SOS, son of sevenless homolog; Grb2, growth factor receptor-bound protein 2; MAP2K, mitogen-activated protein kinase kinase; MAPK, mitogen-activated protein kinase; PI3K, phosphatidylinositol 3 kinase; PKC, protein kinase C; AKT, v-akt murine thymoma viral oncogene homolog; PTEN, phosphatase and tensin homolog; Bcl XL, B-cell lymphoma extra large.
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