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Nat Rev Cancer. 2018 Jul;18(7):452-464. doi: 10.1038/s41568-018-0005-8.

Revisiting the role of ABC transporters in multidrug-resistant cancer.

Author information

1
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
2
National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
3
Division of Hematology/Oncology, Department of Medicine, Columbia University/New York Presbyterian Hospital, Manhattan, NY, USA.
4
James J. Peters VA Medical Center, Bronx, NY, USA.
5
Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. mgottesman@nih.gov.

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.

PMID:
29643473
PMCID:
PMC6622180
DOI:
10.1038/s41568-018-0005-8
[Indexed for MEDLINE]
Free PMC Article

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