Characterization, further analysis and inhibition of the hedgehog signaling pathway during carcinogenesis of cholangiocellular carcinoma, with focus on precursor lesions and identification of tumor-iniating cells.

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Cholangiocarcinoma (CC) is the second most common primary liver tumor worldwide. Incidence and mortality are rising. The only curative treatment of CCs is surgical resection, but most patients are not diagnosed until a metastatic stage. Current chemotherapies have only limited advantage and median survival is just slightly improved. The CC carcinogenesis is a multistep process that leads to the ignition and cholestasis to cell damage and the consequent excessive of cell proliferation. Here, the Hedgehog signaling pathway plays an important role. Also, tumor-initiating cells are discussed to be the origin of cancer. So far a detailed characterization and inhibition of the hedgehog signaling pathway during in vivo carcinogenesis of intrahepatic CCs and its precursors has not been carried out. There is alsolacking knowledge of the significance and the inhibition of tumor -initiating cells for this disease. Finally, the influence of a Hedgehog inhibition on therapeutic efficacy under hypoxic conditions has not been adequately studied, and should be the research objectives of this project among others.