ABC transporters as mediators of drug resistance and contributors to cancer cell biology. (May 2016)

• Record Type: Journal Article
• Authors: Fletcher, Jamie I.; Williams, Rebekka T.; Henderson, Michelle J.; Norris, Murray D.; Haber, Michelle
• Is Part Of: Drug resistance updates. Volume 26(2016)
• Page Start: 1
• Page End: 9
• Publication Date: 2016-05
• Subjects: Multidrug resistance -- Tumorigenesis -- Ovarian cancer -- Neuroblastoma -- Endogenous substrates; Drug resistance in cancer cells -- Periodicals; Cancer -- Chemotherapy -- Periodicals; 616.994061
• DOI: 10.1016/j.drup.2016.03.001
• Languages: English
• ISSNs: 1368-7646

Abstract

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.