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Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

Molecular mechanism of multidrug resistance in tumor cells

I B Roninson

    Clinical Physiology and Biochemistry
    |January 1, 1987
    PubMed

    Insights

    Multidrug resistance in cancer chemotherapy is a major challenge. A newly identified gene, mdr1, and its protein product, P-glycoprotein, are responsible for this resistance by pumping drugs out of tumor cells.

    Area of Science:

    • Molecular Biology
    • Cancer Research
    • Cell Biology

    Background:

    • Simultaneous resistance to multiple lipophilic cytotoxic drugs is a significant obstacle in cancer chemotherapy.
    • Understanding the molecular mechanisms underlying multidrug resistance is crucial for developing effective treatments.

    Purpose of the Study:

    • To review recent molecular biological studies identifying the gene responsible for multidrug resistance in human tumor cells.
    • To elucidate the role of this gene and its protein product in conferring multidrug resistance.

    Main Methods:

    • Identification and cloning of the multidrug resistance gene (mdr1).
    • Gene transfer and expression assays to confirm the gene's necessity and sufficiency for resistance.
    • Analysis of P-glycoprotein homology with bacterial transport proteins.

    Main Results:

    • The mdr1 gene was identified and cloned, and is overexpressed in all analyzed multidrug-resistant cell lines.
    • Gene transfer studies confirmed mdr1 is necessary and sufficient for multidrug resistance.
    • The mdr1 gene product, P-glycoprotein, functions as an energy-dependent efflux pump removing drugs from cells.

    Conclusions:

    • The mdr1 gene and its P-glycoprotein product are key mediators of multidrug resistance in human tumors.
    • Understanding the mdr system offers potential targets for overcoming chemotherapy resistance.
    • Further research into the mdr system's function in normal cells and clinical implications is warranted.

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