title: Molecular Bases of Chemoresistance in Cholangiocarcinoma.
abstract: The multidrug resistance (MDR) phenotype accounts for the poor response of cholangiocarcinoma to available antitumor drugs. This is an important limitation to the use of pharmacological approaches, both as adjuvant therapies and for treating advanced CCA when surgical removal is not possible. MDR is the result of a complex combination of defense mechanisms against toxic compounds already present in cholangiocytes, which play a role in the physiology of these cells by protecting the biliary epithelium from the toxins reaching the biliary tree with the blood that perfuses this tissue, or that are secreted by hepatocytes into bile, to which cholangiocytes are exposed. These mechanisms of chemoresistance (MOC) are also present, usually with enhanced efficacy, in tumors derived from cholangiolar cells. The present review article is an update of the state-of-the-art regarding the MOC involved in the poor response of CCA to antitumor drugs. These MOC have been classified as: changes in the amount of drug in the cells due to decreased uptake (MOC-1a) or enhanced efflux (MOC-1b); altered proportions between prodrug, active drug and inactive metabolites (MOC-2); changes in the molecular targets of antitumor drugs (MOC-3); an enhanced ability of tumor cells to repair drug-induced DNA damage (MOC-4), and an impaired apoptosis/survival balance (MOC-5).
authors.affiliation: Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain.
authors.forename: Jose J G
authors.initials: JJG
authors.lastname: Marin
authors.affiliation: Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: Lozano
authors.affiliation: Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Briz
authors.affiliation: Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), Biomedical Research Institute of Salamanca (IBSAL), University of Salamanca, Salamanca, Spain.
authors.forename: Ruba
authors.initials: R
authors.lastname: Al-Abdulla
authors.affiliation: Centre for the Study of Liver and Gastrointestinal Diseases (CIBERehd), National Institute of Health Carlos III, Madrid, Spain.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Serrano
authors.affiliation: Centre for the Study of Liver and Gastrointestinal Diseases (CIBERehd), National Institute of Health Carlos III, Madrid, Spain.
authors.forename: Rocio I R
authors.initials: RIR
authors.lastname: Macias
mesh_terms: D001650:Bile Duct Neoplasms / Q000188:drug therapy / Q000235:genetics*; D002470:Cell Survival; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000235:genetics*; D004260:DNA Repair; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans
keywords: Chemotherapy; drug metabolism; drug transport; liver cancer; pharmacology; treatment; tumor