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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
18:57

Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers

Published on: October 17, 2013

Transport proteins in drug resistance: biology and approaches to circumvention

P R Twentyman

    Journal of Internal Medicine. Supplement
    |January 1, 1997
    PubMed

    Insights

    Two key proteins, P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP), contribute to cancer therapy resistance by affecting drug transport. Strategies to overcome this drug resistance are currently in clinical trials.

    Area of Science:

    • Biochemistry
    • Molecular Biology
    • Oncology

    Background:

    • Clinical resistance to cytotoxic therapy is a significant challenge in treating malignant diseases.
    • P-glycoprotein (Pgp) and multidrug resistance-associated protein (MRP) are implicated as major transport proteins in this resistance.
    • These proteins are often overexpressed in various leukaemias and other cancers.

    Purpose of the Study:

    • To investigate the role of Pgp and MRP in clinical drug resistance.
    • To understand the mechanisms of cellular drug efflux and sequestration mediated by these transporters.
    • To explore strategies for circumventing multidrug resistance in cancer therapy.

    Main Methods:

    • Analysis of Pgp and MRP expression levels in malignant diseases.
    • Investigation of the localization of these proteins on cellular and vesicular membranes.
    • Assessment of the dependence of MRP function on intracellular glutathione levels.

    Main Results:

    • Pgp and MRP facilitate drug resistance through mechanisms of cellular drug efflux and vesicular sequestration.
    • Expression of these proteins is variable but significant in certain leukaemias and other cancers.
    • MRP's transport activity is influenced by intracellular glutathione concentrations.

    Conclusions:

    • Pgp and MRP are critical determinants of clinical resistance to chemotherapy.
    • Targeting these drug efflux pumps and understanding their regulation are key to improving cancer treatment efficacy.
    • Novel strategies aimed at overcoming Pgp- and MRP-mediated resistance are under active clinical investigation.

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