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Pharmacogenetics of ATP-Binding Cassette Transporters and Clinical Implications

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Multi-Drug Resistance in Cancer

Part of the book series: Methods in Molecular Biology ((MIMB,volume 596))

Abstract

Drug resistance is a severe limitation of chemotherapy of various malignancies. In particular efflux transporters of the ATP-binding cassette family such as ABCB1 (P-glycoprotein), the ABCC (multidrug resistance-associated protein) family, and ABCG2 (breast cancer resistance protein) have been identified as major determinants of chemoresistance in tumor cells. Bioavailability depends not only on the activity of drug metabolizing enzymes but also to a major extent on the activity of drug transport across biomembranes. They are expressed in the apical membranes of many barrier tissues such as the intestine, liver, blood–brain barrier, kidney, placenta, testis, and in lymphocytes, thus contributing to plasma, liquor, but also intracellular drug disposition. Since expression and function exhibit a broad variability, it was hypothesized that hereditary variances in the genes of membrane transporters could explain at least in part interindividual differences of pharmacokinetics of a variety of anticancer drugs and many others contributing to the clinical outcome of certain leukemias and further malignancies.

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Authors and Affiliations

  1. Institute of Experimental and Clinical Pharmacology, University of Kiel, Kiel, Germany

    Ingolf Cascorbi & Sierk Haenisch

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  1. Ingolf Cascorbi
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  2. Sierk Haenisch
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Correspondence to Ingolf Cascorbi .

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  1. College of Life Sciences, Nankai University, Weijin Rd. 94, Tianjin, 300071, China, People's Republic

    Jun Zhou

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Cascorbi, I., Haenisch, S. (2010). Pharmacogenetics of ATP-Binding Cassette Transporters and Clinical Implications. In: Zhou, J. (eds) Multi-Drug Resistance in Cancer. Methods in Molecular Biology, vol 596. Humana Press. https://doi.org/10.1007/978-1-60761-416-6_6

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