Impact of Aberrant β-Catenin Pathway on Cholangiocarcinoma Heterogeneity
Elisa Lozano,
Paula Sanchon-Sanchez,
Ana Morente-Carrasco,
Luis Miguel Chinchilla-Tábora,
José L. Mauriz,
Paula Fernández-Palanca,
Jose J. G. Marin,
Rocio I. R. Macias
Affiliations
Elisa Lozano
Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, Spain
Paula Sanchon-Sanchez
Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, Spain
Ana Morente-Carrasco
Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, Spain
Luis Miguel Chinchilla-Tábora
Pathology Service, University Hospital and IBSAL, 37007 Salamanca, Spain
José L. Mauriz
Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, 28029 Madrid, Spain
Paula Fernández-Palanca
Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health, 28029 Madrid, Spain
Jose J. G. Marin
Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, Spain
Rocio I. R. Macias
Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, Spain
The poor prognosis of most cases of advanced cholangiocarcinoma (CCA) constitutes a severe problem in modern oncology, which is aggravated by the fact that the incidence of this liver cancer is increasing worldwide and is often diagnosed late, when surgical removal is not feasible. The difficulty of dealing with this deadly tumor is augmented by the heterogeneity of CCA subtypes and the complexity of mechanisms involved in enhanced proliferation, apoptosis avoidance, chemoresistance, invasiveness, and metastasis that characterize CCA. Among the regulatory processes implicated in developing these malignant traits, the Wnt/β-catenin pathway plays a pivotal role. Alteration of β-catenin expression and subcellular localization has been associated with worse outcomes in some CCA subtypes. This heterogeneity, which also affects cellular and in vivo models commonly used to study CCA biology and anticancer drug development, must be taken into account for CCA investigation to more accurately extrapolate basic laboratory research to the clinical situation. A better understanding of the altered Wnt/β-catenin pathway in relationship with the heterogeneous forms of CCA is mandatory for developing novel diagnostic tools and therapeutic strategies for patients suffering from this lethal disease.
