ABC transporters as mediators of drug resistance and contributors to cancer cell biology

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• 作者：Jamie I. Fletcher ; Rebekka T. Williams ; Michelle J. Henderson ; Murray D. Norris ; Michelle Haber ; ^{mhaber@ccia.unsw.edu.au" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Multidrug resistance ; Tumorigenesis ; Ovarian cancer ; Neuroblastoma ; Endogenous substrates
• 刊名：Drug Resistance Updates
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：26
• 期：Complete
• 页码：1-9
• 全文大小：1458 K

文摘

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.