AuroraB kinase as a potential therapeutic target for biliary tract carcinoma

1819 Aurora kinases are over-expressed in a variety of cancers and strategies targeting aurora kinases are intensively studied as potential anti-cancer treatment. In this study we sought to explore the expression pattern of auroraB kinase in biliary tract carcinoma and the potential of using aurora kinase inhibition for the treatment of biliary tract carcinoma, which is resistant to most conventional cytotoxic agents. Archival tumor tissue was obtained from patients who underwent operation as an attempt of definitive treatment. Immunohistochemical staining with rabbit anti-auroraB kinase antibody (NB100-294, Novus) was used to evaluate the extent of nuclear staining. We tested the growth-inhibitory effect of VE-465, a small-molecule aurora kinase inhibitor provided by Merck, in a biliary tract carcinoma cell line HuCCT1. Cell viability was measured by trypan blue staining. Protein expression was evaluated by western blotting and immunocytochemistry. DNA content and apoptosis were measured by flow cytometry. A total of 162 patients with biliary tract carcinoma (74 intrahepatic cholangiocarcinoma, 49 extrahepatic bile duct carcinoma, and 39 gallbladder carcinoma) were evaluated. Nuclear expression of auroraB kinase, defined as moderate to strong nuclear staining in more than 10% of tumor cells, was found in 45 (27.8%) patients, including 19 of 64 stage I/II disease and 26 of 98 stage III/IV disease (p = 0.66). The median overall survival for patients with and without nuclear expression of auroraB kinase was 11.4 months and 17.7 months, respectively (p=0.03) Multi-variate analysis indicated that tumor stage and nuclear expression of auroraB kinase were significant prognostic factor (p