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ABC Transporter-Mediated Multidrug-Resistant Cancer

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Drug Transporters in Drug Disposition, Effects and Toxicity

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1141))

Abstract

ATP-binding cassette (ABC) transporters are involved in active pumping of many diverse substrates through the cellular membrane. The transport mediated by these proteins modulates the pharmacokinetics of many drugs and xenobiotics. These transporters are involved in the pathogenesis of several human diseases. The overexpression of certain transporters by cancer cells has been identified as a key factor in the development of resistance to chemotherapeutic agents. In this chapter, the localization of ABC transporters in the human body, their physiological roles, and their roles in the development of multidrug resistance (MDR) are reviewed. Specifically, P-glycoprotein (P-GP), multidrug resistance-associated proteins (MRPs), and breast cancer resistance protein (BCRP/ABCG2) are described in more detail. The potential of ABC transporters as therapeutic targets to overcome MDR and strategies for this purpose are discussed as well as various explanations for the lack of efficacy of ABC drug transporter inhibitors to increase the efficiency of chemotherapy.

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Acknowledgments

We thank Dr. Charles R. Ashby, Jr. and George Leiman for their editorial assistance. SVA was supported by the Intramural Research Program of the National Institutes of Health, the National Cancer Institute, and the Center for Cancer Research.

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  1. Suneet Shukla

    Present address: Division of Biopharmaceutics, Office of New Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA

Authors and Affiliations

  1. Department of Pharmacy Practice, Faculty of Pharmacy, Yarmouk University, Irbid, Jordan

    Haneen Amawi

  2. Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore, Singapore

    Hong-May Sim

  3. Department of Pharmacology and Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA

    Amit K. Tiwari

  4. Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Suresh V. Ambudkar & Suneet Shukla

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  1. School of Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China

    Xiaodong Liu

  2. Shanghai Institute of Materia Medica, Chinese Academy of Science, Shanghai, Shanghai, China

    Guoyu Pan

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Amawi, H., Sim, HM., Tiwari, A.K., Ambudkar, S.V., Shukla, S. (2019). ABC Transporter-Mediated Multidrug-Resistant Cancer. In: Liu, X., Pan, G. (eds) Drug Transporters in Drug Disposition, Effects and Toxicity. Advances in Experimental Medicine and Biology, vol 1141. Springer, Singapore. https://doi.org/10.1007/978-981-13-7647-4_12

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