Medical treatments: in association or alone, their role and their future perspectives: novel molecular-targeted therapy for hepatocellular carcinoma.
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.
Tanaka
Shinji
S
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
Arii
Shigeki
S
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
D004273:DNA, Neoplasm; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases