Perspective | Published:

Opinion

Revisiting the role of ABC transporters in multidrug-resistant cancer

Nature Reviews Cancervolume 18pages452464 (2018) | Download Citation

Abstract

Most patients who die of cancer have disseminated disease that has become resistant to multiple therapeutic modalities. Ample evidence suggests that the expression of ATP-binding cassette (ABC) transporters, especially the multidrug resistance protein 1 (MDR1, also known as P-glycoprotein or P-gp), which is encoded by ABC subfamily B member 1 (ABCB1), can confer resistance to cytotoxic and targeted chemotherapy. However, the development of MDR1 as a therapeutic target has been unsuccessful. At the time of its discovery, appropriate tools for the characterization and clinical development of MDR1 as a therapeutic target were lacking. Thirty years after the initial cloning and characterization of MDR1 and the implication of two additional ABC transporters, the multidrug resistance-associated protein 1 (MRP1; encoded by ABCC1)), and ABCG2, in multidrug resistance, interest in investigating these transporters as therapeutic targets has waned. However, with the emergence of new data and advanced techniques, we propose to re-evaluate whether these transporters play a clinical role in multidrug resistance. With this Opinion article, we present recent evidence indicating that it is time to revisit the investigation into the role of ABC transporters in efficient drug delivery in various cancer types and at the blood–brain barrier.

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Acknowledgements

The authors appreciate the help of S. Lusvarghi with figures and the editorial assistance of G. Leiman. This research was supported by the Intramural Research Program of the National Institutes of Health, US National Cancer Institute. The content of this publication does not necessarily reflect the views of policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products or organizations imply endorsement by the US government.

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Affiliations

  1. Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    • Robert W. Robey
    • , Kristen M. Pluchino
    •  & Michael M. Gottesman
  2. National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA

    • Matthew D. Hall
  3. Division of Hematology/Oncology, Department of Medicine, Columbia University/New York Presbyterian Hospital, Manhattan, NY, USA

    • Antonio T. Fojo
    •  & Susan E. Bates
  4. James J. Peters VA Medical Center, Bronx, NY, USA

    • Antonio T. Fojo
    •  & Susan E. Bates

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Contributions

R.W.R. researched the data for the article, provided substantial contributions to discussions of its content, wrote the article and undertook review and/or editing of the manuscript before submission. K.M.P. researched data for the article. M.D.H. and A.T.F. provided substantial contributions to discussions of the content and wrote the article. S.E.B. and M.M.G. provided substantial contributions to discussions of the content, wrote the article and reviewed and/or edited the manuscript before submission.

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The authors declare no competing interests.

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Correspondence to Michael M. Gottesman.

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https://doi.org/10.1038/s41568-018-0005-8