title: Multidrug Resistance Proteins (MRPs) and Cancer Therapy.
abstract: The ATP-binding cassette (ABC) transporters are members of a protein superfamily that are known to translocate various substrates across membranes, including metabolic products, lipids and sterols, and xenobiotic drugs. Multidrug resistance proteins (MRPs) belong to the subfamily C in the ABC transporter superfamily. MRPs have been implicated in mediating multidrug resistance by actively extruding chemotherapeutic substrates. Moreover, some MRPs are known to be essential in physiological excretory or regulatory pathways. The importance of MRPs in cancer therapy is also implied by their clinical insights. Modulating the function of MRPs to re-sensitize chemotherapeutic agents in cancer therapy shows great promise in cancer therapy; thus, multiple MRP inhibitors have been developed recently. This review article summarizes the structure, distribution, and physiological as well as pharmacological function of MRP1-MRP9 in cancer chemotherapy. Several novel modulators targeting MRPs in cancer therapy are also discussed.
authors.affiliation: College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY, 11439, USA, yunkai.zhang12@stjohns.edu.
authors.forename: Yun-Kai
authors.initials: YK
authors.lastname: Zhang
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Wang
authors.forename: Pranav
authors.initials: P
authors.lastname: Gupta
authors.forename: Zhe-Sheng
authors.initials: ZS
authors.lastname: Chen
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001692:Biological Transport / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D027425:ATP-Binding Cassette, Sub-Family C Proteins
references.citation: Cancer Res. 2002 Nov 1;62(21):6172-7
references.pmid: 12414644
references.citation: Anticancer Res. 2010 Dec;30(12):5189-94
references.pmid: 21187511
references.citation: Biochem Biophys Res Commun. 2008 Jan 4;365(1):29-34
references.pmid: 17980150
references.citation: J Pharmacol Exp Ther. 2006 Oct;319(1):459-67
references.pmid: 16857726
references.citation: Hepatology. 2001 Apr;33(4):783-91
references.pmid: 11283840
references.citation: Chem Biol Interact. 2014 Dec 5;224:36-41
references.pmid: 25451572
references.citation: Biochem Biophys Res Commun. 2001 Nov 9;288(4):933-9
references.pmid: 11688999
references.citation: Cancer Res. 2011 May 15;71(10):3649-57
references.pmid: 21576088
references.citation: BMC Urol. 2009;9:6
references.pmid: 19552816
references.citation: Hepatology. 1999 Apr;29(4):1156-63
references.pmid: 10094960
references.citation: Annu Rev Pharmacol Toxicol. 2014;54:95-117
references.pmid: 24050699
references.citation: Biochem Pharmacol. 2005 Oct 1;70(7):1088-95
references.pmid: 16099435
references.citation: Mol Pharmacol. 2005 Jul;68(1):160-8
references.pmid: 15814571
references.citation: Curr Drug Metab. 2004 Feb;5(1):21-53
references.pmid: 14965249
references.citation: J Biol Chem. 2000 Dec 15;275(50):39617-24
references.pmid: 10978330
references.citation: J Biol Chem. 2003 Jun 27;278(26):23538-44
references.pmid: 12702717
references.citation: J Clin Oncol. 2007 Apr 20;25(12):1545-52
references.pmid: 17442998
references.citation: J Mol Histol. 2005 Mar;36(3):167-70
references.pmid: 15900406
references.citation: J Am Soc Nephrol. 2002 Mar;13(3):595-603
references.pmid: 11856762
references.citation: Mol Pharmacol. 2003 May;63(5):1094-103
references.pmid: 12695538
references.citation: Exp Oncol. 2011 Mar;33(1):42-6
references.pmid: 21423094
references.citation: Drug Metab Dispos. 2015 Jan;43(1):93-9
references.pmid: 25349122
references.citation: Mol Pharmacol. 2005 Feb;67(2):545-57
references.pmid: 15537867
references.citation: Br J Pharmacol. 2014 Dec;171(24):5845-57
references.pmid: 25164592
references.citation: Cancer Lett. 2001 Jan 26;162(2):181-91
references.pmid: 11146224
references.citation: Biochem Pharmacol. 2010 Mar 15;79(6):817-24
references.pmid: 19883630
references.citation: Physiol Rev. 2006 Jul;86(3):849-99
references.pmid: 16816140
references.citation: Proc Natl Acad Sci U S A. 2002 May 14;99(10):6997-7002
references.pmid: 12011458
references.citation: J Natl Cancer Inst. 2000 Dec 6;92(23):1934-40
references.pmid: 11106685
references.citation: Oncol Rep. 2009 Jan;21(1):263-8
references.pmid: 19082471
references.citation: Clin Cancer Res. 2001 Jun;7(6):1798-804
references.pmid: 11410522
references.citation: Curr Opin Struct Biol. 2007 Aug;17(4):412-8
references.pmid: 17723295
references.citation: Oncotarget. 2015 Jan 1;6(1):510-21
references.pmid: 25402202
references.citation: Mol Pharmacol. 2002 Dec;62(6):1321-31
references.pmid: 12435799
references.citation: Cancer Res. 1999 Jan 1;59(1):175-82
references.pmid: 9892204
references.citation: Blood. 2010 Feb 25;115(8):1632-9
references.pmid: 19897579
references.citation: PLoS One. 2009;4(9):e7258
references.pmid: 19789626
references.citation: J Bioenerg Biomembr. 2011 Oct;43(5):465-71
references.pmid: 21748403
references.citation: Int J Cancer. 2000 Apr 1;86(1):95-100
references.pmid: 10728601
references.citation: BMC Struct Biol. 2013;13:7
references.pmid: 23641929
references.citation: Neuropediatrics. 2008 Aug;39(4):211-8
references.pmid: 19165709
references.citation: Oncologist. 2004;9 Suppl 3:10-5
references.pmid: 15163842
references.citation: Histochem Cell Biol. 2005 Jun;123(4-5):517-28
references.pmid: 15889270
references.citation: Biochem Pharmacol. 2008 Apr 15;75(8):1659-69
references.pmid: 18336795
references.citation: J Exp Ther Oncol. 2004 Oct;4(3):239-46
references.pmid: 15724843
references.citation: Curr Pharm Biotechnol. 2011 Apr;12(4):570-94
references.pmid: 21118094
references.citation: J Biol Chem. 2001 May 11;276(19):16076-82
references.pmid: 11279022
references.citation: Cancer Cell Int. 2005 Jul 24;5(1):22
references.pmid: 16042792
references.citation: Int J Cancer. 2005 Sep 20;116(5):824-9
references.pmid: 15849751
references.citation: J Biol Chem. 2011 Mar 4;286(9):7202-13
references.pmid: 21177244
references.citation: Br J Cancer. 2000 Aug;83(3):375-83
references.pmid: 10917554
references.citation: Breast Cancer Res Treat. 2011 Oct;129(3):993-9
references.pmid: 21655989
references.citation: Mutagenesis. 2012 Mar;27(2):187-96
references.pmid: 22294766
references.citation: Cancer Res. 2001 Oct 1;61(19):7225-32
references.pmid: 11585759
references.citation: Cancer Res. 2002 Jun 1;62(11):3144-50
references.pmid: 12036927
references.citation: J Biol Chem. 2003 Aug 8;278(32):29509-14
references.pmid: 12764137
references.citation: Breast Cancer Res Treat. 2013 Feb;137(3):773-82
references.pmid: 23288347
references.citation: Mol Cancer Ther. 2007 Jan;6(1):122-7
references.pmid: 17237272
references.citation: Neuroscience. 2006;137(4):1247-57
references.pmid: 16359813
references.citation: Clin Cancer Res. 2002 Dec;8(12):3767-75
references.pmid: 12473588
references.citation: Cancer Sci. 2010 Nov;101(11):2404-10
references.pmid: 20718756
references.citation: Cancer Res. 2005 May 15;65(10):4425-30
references.pmid: 15899835
references.citation: Anticancer Res. 2007 Jul-Aug;27(4B):2115-20
references.pmid: 17695494
references.citation: Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7476-81
references.pmid: 10840050
references.citation: Eur J Pharm Sci. 2014 Oct 1;62:189-96
references.pmid: 24909729
references.citation: Br J Cancer. 2014 Aug 12;111(4):696-707
references.pmid: 24937672
references.citation: Acta Histochem Cytochem. 2014 Jun 28;47(3):85-94
references.pmid: 25320405
references.citation: Cancer Sci. 2012 Aug;103(8):1531-7
references.pmid: 22578167
references.citation: Int J Mol Sci. 2012;13(6):6757-71
references.pmid: 22837662
references.citation: J Med Chem. 2009 Feb 26;52(4):1214-8
references.pmid: 19193010
references.citation: J Biol Chem. 2007 Jul 20;282(29):20999-1004
references.pmid: 17540771
references.citation: Hepatology. 2006 May;43(5):1013-21
references.pmid: 16628672
references.citation: Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6914-9
references.pmid: 10359813
references.citation: Pediatr Hematol Oncol. 2014 Mar;31(2):169-77
references.pmid: 24552501
references.citation: PLoS One. 2009;4(10):e7520
references.pmid: 19841739
references.citation: Exp Dermatol. 2014 Apr;23(4):247-52
references.pmid: 24533866
references.citation: Exp Mol Pathol. 2012 Feb;92(1):44-9
references.pmid: 22037714
references.citation: PLoS One. 2013;8(2):e55576
references.pmid: 23393594
references.citation: Mol Pharmacol. 2000 Mar;57(3):634-41
references.pmid: 10692506
references.citation: AAPS PharmSci. 2002;4(3):E14
references.pmid: 12423063
references.citation: Cancer Res. 2004 Jul 15;64(14):4927-30
references.pmid: 15256465
references.citation: FEBS J. 2011 Sep;278(18):3226-45
references.pmid: 21740521
references.citation: Int J Cancer. 2001 Nov15;94(4):492-9
references.pmid: 11745434
references.citation: Mol Cancer Ther. 2014 Mar;13(3):714-23
references.pmid: 24431074
references.citation: Biochem J. 2012 Sep 1;446(2):291-300
references.pmid: 22676135
references.citation: Mol Pharmacol. 2003 Feb;63(2):351-8
references.pmid: 12527806
references.citation: Public Health Rep. 2006 Nov-Dec;121(6):646-9
references.pmid: 17278398
references.citation: Biochem Biophys Res Commun. 2000 Aug 2;274(2):297-301
references.pmid: 10913334
references.citation: Clin Cancer Res. 2005 Dec 15;11(24 Pt 1):8661-8
references.pmid: 16361551
references.citation: Curr Med Chem. 2011;18(3):439-81
references.pmid: 21143116
references.citation: Cancer Cell. 2002 Aug;2(2):117-25
references.pmid: 12204532
references.citation: Prostate Cancer Prostatic Dis. 2000 Aug;3(2):66-75
references.pmid: 12497102
references.citation: Toxicol Appl Pharmacol. 2005 May 1;204(3):216-37
references.pmid: 15845415
references.citation: Oncol Rep. 2013 Jun;29(6):2479-85
references.pmid: 23525656
references.citation: Biochem Pharmacol. 2009 Mar 15;77(6):993-1001
references.pmid: 19150344
references.citation: Biochem Pharmacol. 2010 Jan 15;79(2):154-61
references.pmid: 19720054
references.citation: J Bioenerg Biomembr. 2001 Dec;33(6):475-9
references.pmid: 11804189
references.citation: J Natl Cancer Inst. 2011 Aug 17;103(16):1236-51
references.pmid: 21799180
references.citation: Drug Metab Dispos. 2008 Mar;36(3):552-60
references.pmid: 18079363
references.citation: Mol Cell Biol. 2004 Sep;24(17):7612-21
references.pmid: 15314169