title: MRP1 and its role in anticancer drug resistance.
abstract: The phenomenon of multidrug resistance (MDR) in cancer is associated with the overexpression of the ATP-binding cassette (ABC) transporter proteins, including multidrug resistance-associated protein 1 (MRP1) and P-glycoprotein. MRP1 plays an active role in protecting cells by its ability to efflux a vast array of drugs to sub-lethal levels. There has been much effort in elucidating the mechanisms of action, structure and substrates and substrate binding sites of MRP1 in the last decade. In this review, we detail our current understanding of MRP1, its clinical relevance and highlight the current environment in the search for MRP1 inhibitors. We also look at the capacity for the rapid intercellular transfer of MRP1 phenotype from spontaneously shed membrane vesicles known as microparticles and discuss the clinical and therapeutic significance of this in the context of cancer MDR.
authors.affiliation: a Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney , Broadway , NSW , Australia.
authors.forename: Jamie F
authors.initials: JF
authors.lastname: Lu
authors.affiliation: a Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney , Broadway , NSW , Australia.
authors.forename: Deep
authors.initials: D
authors.lastname: Pokharel
authors.affiliation: a Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney , Broadway , NSW , Australia.
authors.forename: Mary
authors.initials: M
authors.lastname: Bebawy
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D049990:Membrane Transport Modulators / Q000494:pharmacology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism
chemical_list: D049990:Membrane Transport Modulators; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C421109:multidrug resistance-associated protein 1
keywords: Microparticles; P-glycoprotein; cancer; intercellular transfer; multidrug resistance; multidrug resistance-associated protein 1; trait dominance