title: Molecular Mechanisms of Cholangiocarcinogenesis: New Potential Targets for Therapy.
abstract: Cholangiocarcinoma (CCA) is a heterogeneous group of dysplastic disorders affecting the biliary epithelium. It is the second most common primary liver tumor which accounts for around 3% of all gastrointestinal cancers. CCA is very deadly due to its aggressiveness, late diagnosis and high chemoresistance. The incidence is increasing worldwide and the therapeutic options are very limited. Radiotherapy, chemotherapy, surgery and/or liver transplantation may be indicated in patients who meet certain criteria, but chances of success are low. There is therefore increasing interest in understanding the molecular mechanisms involved in the pathogenesis of this cancer type and in identifying new targets for therapy. Current strategies are based on targeting key signaling pathways involved in proliferation, survival, apoptosis and migration. In this review, the most relevant molecular mechanisms involved in the pathogenesis of CCA are discussed and the main preclinical and clinical studies are highlighted. Moreover, future directions in basic and clinical research are indicated.
authors: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain.
authors: Oihane
authors: O
authors: Erice
authors: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain.
authors: Maite
authors: M
authors: Merino-Azpitarte
authors: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain.
authors: Ander
authors: A
authors: Arbelaiz
authors: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain.
authors: Maria
authors: M
authors: Gutierrez-Larranaga
authors: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain.
authors: Raul
authors: R
authors: Jimenez-Aguero
authors: IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
authors: Maria J
authors: MJ
authors: Perugorria
authors: National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, Instituto de Salud Carlos III), Madrid, Spain.
authors: Luis
authors: L
authors: Bujanda
authors: Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, Paseo del Dr. Begiristain s/n, E-20014, San Sebastian, Spain.
authors: Jesus M
authors: JM
authors: Banales
mesh_terms: D000818:Animals; D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D002986:Clinical Trials as Topic; D005260:Female; D053263:Gene Regulatory Networks; D006801:Humans; D015994:Incidence; D008297:Male; D058990:Molecular Targeted Therapy
keywords: Biliary epithelium; cancer; cholangiocarcinoma; molecular mechanisms; pathogenesis; stroma; therapy