Multidrug resistance efflux transporter (MDR transporter)

Multidrug resistance (MDR) efflux transporters are a group of transmembrane proteins, primarily within the ATP-binding cassette (ABC) superfamily, that actively transport a diverse range of hydrophobic substrates out of cells using energy derived from ATP hydrolysis [1][4]. The most prominent members include P-glycoprotein (ABCB1), Multidrug Resistance-associated Protein 1 (ABCC1), and Breast Cancer Resistance Protein (ABCG2) [1]. These transporters are naturally expressed in physiological barriers such as the blood-brain barrier, gastrointestinal tract, and kidneys, where they serve a protective role by limiting the entry of toxins and facilitating the excretion of xenobiotics [2]. In clinical oncology, the over-expression of these transporters in tumor cells is a hallmark of multidrug resistance, as they effectively pump out various chemotherapeutic agents, including anthracyclines, taxanes, and vinca alkaloids, thereby reducing treatment efficacy [3]. Beyond cancer, they play roles in drug resistance in epilepsy and are involved in the clearance of metabolic waste like amyloid-beta in the brain [2]. While they are significant targets for drug development aimed at reversing chemoresistance, therapeutic strategies must carefully manage the high risk of drug-drug interactions and potential neurotoxicity resulting from the inhibition of these transporters at the blood-brain barrier [4]. Sources: [1] Robey, R. W., et al. (2018). "ABC transporters: biological insights and structure-function relationships." Nature Reviews Cancer, 18(7), 452-464. [2] Miller, D. S. (2010). "ABC transporters at the blood-brain barrier." Trends in Molecular Medicine, 16(9), 398-407. [3] Choi, Y. H., & Yu, A. M. (2014). "ABC transporters in multidrug resistance and pharmacokinetics, and strategies for drug development." Current Pharmaceutical Design, 20(5), 793-807. [4] Giacomini, K. M., et al. (2010). "Membrane transporters in drug development." Nature Reviews Drug Discovery, 9(3), 215-236.

Other names

ABC transportersMultidrug resistance proteinsXenobiotic efflux pumpsATP-binding cassette transportersP-glycoprotein-like transporters

Inhibition of ATP-binding cassette (ABC) transporters to prevent the active efflux of substrate drugs, thereby increasing their intracellular concentration and efficacy, particularly in resistant cancer cells [1][3].