Revisiting the role of efflux pumps in multidrug-resistant cancer

By R. Robey, Kristen M. Pluchino, Matthew D. Hall, A. Fojo, S. Bates, Michael M. Gottesman. Nature Reviews. Cancer, 2018

1,590 citations recorded by the source corpus.

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. This Opinion argues for a new look at the role of ABC transporters in cancer multidrug resistance to push forward their clinical application as biomarkers and as targets in combination therapies in order to improve anticancer drug efficiency.

Subfields: Infectious Diseases, Oncology, Pediatrics, Perinatology and Child Health

View Paper: https://www.semanticscholar.org/paper/81ec02b4a6d96f187580806d7affc7fcc5f32e03

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Citations in the corpus

• Targeting p53 pathways: mechanisms, structures and advances in therapy (2023, background): “Multidrug resistance protein 1 (MDR1, also known as P-glycoprotein), encoded by ATP-binding cassette subfamily B member 1, has been shown to be resistant to cytotoxicity and chemotherapy.(254) In p53 mutant R248Q-expressing Hep3B cells, expression and activity of the multiple drug resistance gene, P”