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

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.

• Authors: Robert W Robey, Kristen M Pluchino, Matthew D Hall, Antonio T Fojo, Susan E Bates, Michael M Gottesman
• Journal: Nature reviews. Cancer (Nat Rev Cancer) Vol. 18 Issue 7 Pg. 452-464 (07 2018) ISSN: 1474-1768 [Electronic] England
• PMID: 29643473 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Review)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters
• Multidrug Resistance-Associated Proteins
• multidrug resistance-associated protein 1

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)
• ATP Binding Cassette Transporter, Subfamily G, Member 2 (genetics)
• ATP-Binding Cassette Transporters (genetics)
• Blood-Brain Barrier
• Drug Resistance, Multiple (genetics)
• Drug Resistance, Neoplasm (genetics)
• Humans
• Molecular Targeted Therapy
• Multidrug Resistance-Associated Proteins (genetics)
• Neoplasms (drug therapy)