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Multidrug Resistance: A Role for Membrane Physics, pH and Drug Transporters

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Molecular Mechanisms of Tumor Cell Resistance to Chemotherapy

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 1))

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Abstract

Cancer is the second cause of mortality worldwide (~8 million death a year) with a cost amounting to ~$900b a year. Early treatment is of paramount importance, and tissue susceptible to becoming cancerous is a target for preventative treatment. Multi-drug resistance (MDR) is a common cause of chemotherapeutic failure in the case of 90 % of metastatic cancer. Different valid theories have been suggested about MDR (drugs transporters, pH, membrane and so on) but there is now a need to provide a unified model concerning all these observations. Herein we show how the alteration in the membrane physical properties mediated by pH changes and the expression of drug transporters are paramount in MDR.

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Abbreviations

ABC:

ATP-binding cassette

MDR:

Multi-drug resistance

NHE1:

The sodium-hydrogen exchanger 1

Pgp:

P-glycoprotein

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No potential conflicts of interest were disclosed.

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Authors and Affiliations

  1. School of Veterinary Medicine and Science, University of Nottingham, College Road, Sutton Bonington, LE12 5RD, UK

    Chloe Daniel & Cyril Rauch

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  1. Chloe Daniel
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  2. Cyril Rauch
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Correspondence to Cyril Rauch .

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Editors and Affiliations

  1. Dept. Microbiology, Immunology &, Molecular Genetics, University of California, Los Angeles, Charles E. Young Dr. E. 609, Los Angeles, 90095, California, USA

    Benjamin Bonavida

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Daniel, C., Rauch, C. (2013). Multidrug Resistance: A Role for Membrane Physics, pH and Drug Transporters. In: Bonavida, B. (eds) Molecular Mechanisms of Tumor Cell Resistance to Chemotherapy. Resistance to Targeted Anti-Cancer Therapeutics, vol 1. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7070-0_2

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