In Vitro and In Vivo Model Systems of Cholangiocarcinoma

Daily clinical practice and recent high-throughput molecular studies have clearly revealed the high phenotypic and molecular heterogeneity of cholangiocarcinoma (CCA). Currently, available treatment options remain limited and often unsatisfactory, making the development of more effective therapies an urgent need for this dismal disease. In an effort to address this challenge, the generation of preclinical models has become paramount to improve our knowledge regarding CCA carcinogenesis and progression and to develop novel treatment options. Several CCA in vitro and in vivo models able to reproduce some of the main pathophysiological and molecular features of CCA have been established. Compared to in vitro systems, experimental CCA animal models may more closely recapitulate the complex cross talk between tumor and stromal cells, a hallmark underlying the high invasiveness that characterizes this malignancy. To date, the repertoire of CCA animal models include carcinogen-based models, genetically engineered models, transposon-based models, and xenograft and syngeneic models. The present chapter summarizes the current knowledge and understanding of preclinical in vitro and in vivo models in CCA, critically reviewing their translational usefulness and limitations.