title: Medical treatments: in association or alone, their role and their future perspectives: novel molecular-targeted therapy for hepatocellular carcinoma.
abstract: Accumulated understanding of the molecular networks in the state of oncogene addiction, i.e., the "Achilles' heel of cancer," has led to the development of novel targeted therapies. Using genome-wide gene expression and network analysis, we have identified "Aurora kinase B" as a unique molecule to predict the lethal recurrence of hepatocellular carcinoma (HCC) even after curative hepatectomy. Comparative genomic hybridization (CGH)-array analysis revealed the genomic instability was closely related to Aurora kinase B expression in HCC. Then, we analyzed the in vitro and in vivo effects of a selective inhibitor of Aurora kinase B on human HCC cells. Treatment with Aurora B inhibitor in vitro resulted in polyploidy and apoptotic cell death. The growth of orthotopic liver tumors was significantly suppressed by the Aurora B inhibitor. Our preclinical studies indicate that Aurora kinase B is a promising molecular target "Achilles' heel" for the treatment of aggressive HCC.
authors: Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, Yushima 1-5-45, Bunkyo-ku, Tokyo 113-8519, Japan. shinji.msrg@tmd.ac.jp
authors: Shinji
authors: S
authors: Tanaka
authors: Shigeki
authors: S
authors: Arii
mesh_terms: D064107:Aurora Kinase B; D064127:Aurora Kinases; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D004273:DNA, Neoplasm / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D058990:Molecular Targeted Therapy / Q000379:methods*; D009364:Neoplasm Recurrence, Local / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D004273:DNA, Neoplasm; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases