Multidrug resistance proteins (MRPs): Structure, function and the overcoming of cancer multidrug resistance.

Jing-Quan Wang, Yuqi Yang, Chao-Yun Cai, Qiu-Xu Teng, Qingbin Cui, Jun Lin, Yehuda G Assaraf, Zhe-Sheng Chen

Journal: Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 2021;54():100743

PMID: 33513557

Full Text on Elsevier Science View on PubMed

Abstract

ATP-binding cassette (ABC) transporters mediate the ATP-driven translocation of structurally and mechanistically distinct substrates against steep concentration gradients. Among the seven human ABC subfamilies namely ABCA-ABCG, ABCC is the largest subfamily with 13 members. In this respect, 9 of the ABCC members are termed "multidrug resistance proteins" (MRPs1-9) due to their ability to mediate cancer multidrug resistance (MDR) by extruding various chemotherapeutic agents or their metabolites from tumor cells. Furthermore, MRPs are also responsible for the ATP-driven efflux of physiologically important organic anions such as leukotriene C, folic acid, bile acids and cAMP. Thus, MRPs are involved in important regulatory pathways. Blocking the anticancer drug efflux function of MRPs has shown promising results in overcoming cancer MDR. As a result, many novel MRP modulators have been developed in the past decade. In the current review, we summarize the structure, tissue distribution, biological and pharmacological functions as well as clinical insights of MRPs. Furthermore, recent updates in MRP modulators and their therapeutic applications in clinical trials are also discussed.

Address: Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA; School of Public Health, Guangzhou Medical University, Guangzhou, Guangdong 511436, China; Department of Cancer Biology, University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.; Department of Anesthesiology, Stony Brook University Health Sciences Center, Stony Brook, NY, 11794, USA.; The Fred Wyszkowski Cancer Research Laboratory, Department of Biology, Technion-Israel Institute of Technology, Haifa, 3200003, Israel.; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA. Electronic address: [email protected].

DOI: 10.1016/j.drup.2021.100743