Hedgehog pathway as a potential treatment target in human cholangiocarcinoma. (15th April 2014)

• Record Type: Journal Article
• Authors: Riedlinger, Dorothee; Bahra, Marcus; Boas‐Knoop, Sabine; Lippert, Steffen; Bradtmöller, Maren; Guse, Katrin; Seehofer, Daniel; Bova, Roberta; Sauer, Igor M; Neuhaus, Peter; Koch, Arend; Kamphues, Carsten
• Is Part Of: Journal of hepato-biliary-pancreatic sciences. Volume 21:Number 8(2014)
• Page Start: 607
• Page End: 615
• Publication Date: 2014-04-15
• Subjects: Liver -- Diseases -- Periodicals; Biliary tract -- Diseases -- Periodicals; Pancreas -- Diseases -- Periodicals; 617.556
• DOI: 10.1002/jhbp.107
• Languages: English
• ISSNs: 1868-6974

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="jhbp107-sec-0001" sec-type="section"> <title>Background</title> <p>Innovative treatment concepts targeting essential signaling pathways may offer new chances for patients suffering from cholangiocarcinoma (CCC). For that, we performed a systematic molecular genetic analysis concerning the Hedgehog activity in human CCC samples and analyzed the effect of Hh inhibition on CCC cells <italic>in vitro</italic> and <italic>in vivo</italic>.</p> </sec> <sec id="jhbp107-sec-0002" sec-type="section"> <title>Methods</title> <p>Activation of the Hh pathway was analyzed in 50 human CCC samples using quantitative polymerase chain reaction (qPCR). The efficacy of Hh inhibition using cyclopamine and BMS‐833923 was evaluated <italic>in vitro</italic>. In addition, the effect of BMS‐833923, alone or in combination with gemcitabine, was analyzed <italic>in vivo</italic> in a murine subcutaneous xenograft model.</p> </sec> <sec id="jhbp107-sec-0003" sec-type="section"> <title>Results</title> <p>Expression analysis revealed a significant activation of the Hh‐signaling pathway in nearly 50% of CCCs. Hh inhibition resulted in a significant decrease in cell proliferation of CCC cells. Moreover, a distinct inhibition of tumor growth could be seen as a result of a combined therapy with BMS‐833923 and gemcitabine in CCC xenografts.</p> </sec> <sec id="jhbp107-sec-0004" sec-type="section"> <title>Conclusion</title> <p>The results of our study suggest that the Hh pathway plays a relevant role at least in a subset of human CCC. Inhibition of this pathway may represent a possible treatment option for CCC patients in which the Hh pathway is activated.</p> </sec> </abstract>