title: ABC transporters as mediators of drug resistance and contributors to cancer cell biology.
abstract: The extrusion of anticancer drugs by members of the ATP-binding cassette (ABC) transporter family is one of the most widely recognized mechanisms of multidrug resistance, and can be considered a hijacking of their normal roles in the transport of xenobiotics, metabolites and signaling molecules across cell membranes. While roles in cancer multidrug resistance have been clearly demonstrated for P-glycoprotein (P-gp), Breast Cancer Resistance Protein (BCRP) and Multidrug Resistance Protein 1 (MRP1), direct evidence for a role in multidrug resistance in vivo is lacking for other family members. A less well understood but emerging theme is the drug efflux-independent contributions of ABC transporters to cancer biology, supported by a growing body of evidence that their loss or inhibition impacts on the malignant potential of cancer cells in vitro and in vivo. As with multidrug resistance, these contributions likely represent a hijacking of normal ABC transporter functions in the efflux of endogenous metabolites and signaling molecules, however they may expand the clinical relevance of ABC transporters beyond P-gp, BCRP and MRP1. This review summarizes established and emerging roles for ABC transporters in cancer, with a focus on neuroblastoma and ovarian cancer, and considers approaches to validate and better understand these roles.
authors.affiliation: Children's Cancer Institute Australia, Lowy Cancer Research Centre, Randwick, NSW, Australia.
authors.forename: Jamie I
authors.initials: JI
authors.lastname: Fletcher
authors.affiliation: Children's Cancer Institute Australia, Lowy Cancer Research Centre, Randwick, NSW, Australia.
authors.forename: Rebekka T
authors.initials: RT
authors.lastname: Williams
authors.affiliation: Children's Cancer Institute Australia, Lowy Cancer Research Centre, Randwick, NSW, Australia.
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Henderson
authors.affiliation: Children's Cancer Institute Australia, Lowy Cancer Research Centre, Randwick, NSW, Australia.
authors.forename: Murray D
authors.initials: MD
authors.lastname: Norris
authors.affiliation: Children's Cancer Institute Australia, Lowy Cancer Research Centre, Randwick, NSW, Australia. Electronic address: mhaber@ccia.unsw.edu.au.
authors.forename: Michelle
authors.initials: M
authors.lastname: Haber
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport / Q000502:physiology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D009447:Neuroblastoma / Q000188:drug therapy / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology
chemical_list: D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents
keywords: Endogenous substrates; Multidrug resistance; Neuroblastoma; Ovarian cancer; Tumorigenesis