Mechanisms and therapeutic potential of inhibiting drug efflux transporters

Bibliography

• Shukla S, Ohnuma S, Ambudkar SV. Improving cancer chemotherapy with modulators of ABC drug transporters. Curr Drug Targets 2011;12:621-30
   PubMed Web of Science ®Google Scholar
• Kaelin WGJr. The concept of synthetic lethality in the context of anticancer therapy. Nat Rev Cancer 2005;5:689-98
   PubMed Web of Science ®Google Scholar
• Matheny CJ, Lamb MW, Brouwer KR, et al. Pharmacokinetic and pharmacodynamic implications of P-glycoprotein modulation. Pharmacotherapy 2001;21:778-96
   PubMed Web of Science ®Google Scholar
• Garberg P. In vitro models of blood-brain barrier. Toxicol In Vitro 2005;19:299-334
   PubMed Web of Science ®Google Scholar
• van Asperen J, Mayer U, van Tellingen O, et al. The functional role of P-glycoprotein in the blood-brain barrier. J Pharm Sci 1997;86:881-4
   PubMed Web of Science ®Google Scholar
• Doyle LA, Yang W, Abruzzo LV, et al. A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA 1998;95:15665-70
   PubMed Web of Science ®Google Scholar
• Scharenberg CW, Harkey MA, Torok-Storb B. The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors. Blood 2002;99:507-12
   PubMed Web of Science ®Google Scholar
• Cole SP, Bhardwaj G, Gerlach JH, et al. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science 1992;258:1650-4
   PubMed Web of Science ®Google Scholar
• Wijnholds J, Scheffer GL, van der Valk M, et al. Multidrug resistance protein 1 protects the oropharyngeal mucosal layer and the testicular tubules against drug-induced damage. J Exp Med 1998;188:797-808
   PubMed Web of Science ®Google Scholar
• Renes J, de Vries EG, Nienhuis EF, et al. ATP- and glutathione-dependent transport of chemotherapeutic drugs by the multidrug resistance protein MRP1. Br J Pharmacol 1999;126:681-8
   PubMed Web of Science ®Google Scholar
• Holohan C, Van Schaeybroeck S, Longley DB, et al. Cancer drug resistance: an evolving paradigm. Nat Rev Cancer 2013;13:714-26
   PubMed Web of Science ®Google Scholar
• Borst P. Cancer drug pan-resistance: pumps, cancer stem cells, quiescence, epithelial to mesenchymal transition, blocked cell death pathways, persisters or what? Open Biol 2012;2:120066
   PubMedGoogle Scholar
• Tiwari AK, Sodani K, Dai CL, et al. Revisiting the ABCs of multidrug resistance in cancer chemotherapy. Curr Pharm Biotechnol 2011;12:570-94
   PubMed Web of Science ®Google Scholar
• Thomas H, Coley HM. Overcoming multidrug resistance in cancer: an update on the clinical strategy of inhibiting p-glycoprotein. Cancer Contr 2003;10:159-65
   PubMedGoogle Scholar
• Triller N, Korosec P, Kern I, et al. Multidrug resistance in small cell lung cancer: expression of P-glycoprotein, multidrug resistance protein 1 and lung resistance protein in chemo-naive patients and in relapsed disease. Lung Cancer 2006;54:235-40
   PubMed Web of Science ®Google Scholar
• Nooter K, Brutel de la Riviere G, Look MP, et al. The prognostic significance of expression of the multidrug resistance-associated protein (MRP) in primary breast cancer. Br J Cancer 1997;76:486-93
   PubMed Web of Science ®Google Scholar
• Zalcberg J, Hu XF, Slater A, et al. MRP1 not MDR1 gene expression is the predominant mechanism of acquired multidrug resistance in two prostate carcinoma cell lines. Prostate Cancer Prostatic Dis 2000;3:66-75
   PubMed Web of Science ®Google Scholar
• Shukla S, Chen ZS, Ambudkar SV. Tyrosine kinase inhibitors as modulators of ABC transporter-mediated drug resistance. Drug Resist Updat 2012;15:70-80
   PubMed Web of Science ®Google Scholar
• Jemnitz K, Heredi-Szabo K, Janossy J, et al. ABCC2/Abcc2: a multispecific transporter with dominant excretory functions. Drug Metab Rev 2010;42:402-36
   PubMed Web of Science ®Google Scholar
• Choi JH, Ahn BM, Yi J, et al. MRP2 haplotypes confer differential susceptibility to toxic liver injury. Pharmacogenet Genomics 2007;17:403-15
   PubMed Web of Science ®Google Scholar
• Han JY, Lim HS, Yoo YK, et al. Associations of ABCB1, ABCC2, and ABCG2 polymorphisms with irinotecan-pharmacokinetics and clinical outcome in patients with advanced non-small cell lung cancer. Cancer 2007;110:138-47
   PubMed Web of Science ®Google Scholar
• Sun N, Sun X, Chen B, et al. MRP2 and GSTP1 polymorphisms and chemotherapy response in advanced non-small cell lung cancer. Cancer Chemother Pharmacol 2010;65:437-46
   PubMed Web of Science ®Google Scholar
• Gillet JP, Gottesman MM. Advances in the molecular detection of ABC transporters involved in multidrug resistance in cancer. Curr Pharm Biotechnol 2011;12:686-92
   PubMed Web of Science ®Google Scholar
• Marki-Zay J, Tauberne Jakab K, Szeremy P, et al. MDR-ABC transporters: biomarkers in rheumatoid arthritis. Clin Exp Rheumatol 2013;31:779-87
   PubMed Web of Science ®Google Scholar
• Kosztyu P, Dolezel P, Vaclavikova R, et al. Can the assessment of ABCB1 gene expression predict its function in vitro? Eur J Haematol 2014. [Epub ahead of print]
   Google Scholar
• Meissner K, Jedlitschky G, Meyer zu Schwabedissen H, et al. Modulation of multidrug resistance P-glycoprotein 1 (ABCB1) expression in human heart by hereditary polymorphisms. Pharmacogenetics 2004;14:381-5
   PubMedGoogle Scholar
• Karaszi E, Jakab K, Homolya L, et al. Calcein assay for multidrug resistance reliably predicts therapy response and survival rate in acute myeloid leukaemia. Br J Haematol 2001;112:308-14
   PubMed Web of Science ®Google Scholar
• Sonneveld P, Schoester M, de Leeuw K. Clinical modulation of multidrug resistance in multiple myeloma: effect of cyclosporine on resistant tumor cells. J Clin Oncol 1994;12:1584-91
   PubMed Web of Science ®Google Scholar
• Szakacs G, Paterson JK, Ludwig JA, et al. Targeting multidrug resistance in cancer. Nat Rev Drug Discov 2006;5:219-34
   PubMed Web of Science ®Google Scholar
• Friedenberg WR, Rue M, Blood EA, et al. Phase III study of PSC-833 (valspodar) in combination with vincristine, doxorubicin, and dexamethasone (valspodar/VAD) versus VAD alone in patients with recurring or refractory multiple myeloma (E1A95): a trial of the Eastern Cooperative Oncology Group. Cancer 2006;106:830-8
   PubMed Web of Science ®Google Scholar
• Dantzig AH, Shepard RL, Law KL, et al. Selectivity of the multidrug resistance modulator, LY335979, for P-glycoprotein and effect on cytochrome P-450 activities. J Pharmacol Exp Ther 1999;290:854-62
   PubMed Web of Science ®Google Scholar
• Ding R, Shi J, Pabon K, et al. Xanthines down-regulate the drug transporter ABCG2 and reverse multidrug resistance. Mol Pharmacol 2012;81:328-37
   PubMed Web of Science ®Google Scholar
• Skupien K, Kostrzewa-Nowak D, Oszmianski J, et al. In vitro antileukaemic activity of extracts from chokeberry (Aronia melanocarpa [Michx] Elliott) and mulberry (Morus alba L.) leaves against sensitive and multidrug resistant HL60 cells. Phytother Res 2008;22:689-94
   PubMed Web of Science ®Google Scholar
• Wu CP, Ohnuma S, Ambudkar SV. Discovering natural product modulators to overcome multidrug resistance in cancer chemotherapy. Curr Pharm Biotechnol 2011;12:609-20
   PubMed Web of Science ®Google Scholar
• Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 2003;23:363-98
   PubMed Web of Science ®Google Scholar
• Shukla S, Zaher H, Hartz A, et al. Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res 2009;26:480-7
   PubMed Web of Science ®Google Scholar
• Cheng AL, Hsu CH, Lin JK, et al. Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 2001;21:2895-900
   PubMed Web of Science ®Google Scholar
• Sharma RA, Gescher AJ, Steward WP. Curcumin: the story so far. Eur J Cancer 2005;41:1955-68
   PubMed Web of Science ®Google Scholar
• Dhillon N, Aggarwal BB, Newman RA, et al. Phase II trial of curcumin in patients with advanced pancreatic cancer. Clin Cancer Res 2008;14:4491-9
   PubMed Web of Science ®Google Scholar
• Choi SU, Ryu SY, Yoon SK, et al. Effects of flavonoids on the growth and cell cycle of cancer cells. Anticancer Res 1999;19:5229-33
   PubMed Web of Science ®Google Scholar
• Morris ME, Zhang S. Flavonoid-drug interactions: effects of flavonoids on ABC transporters. Life Sci 2006;78:2116-30
   PubMed Web of Science ®Google Scholar
• Boumendjel A, Di Pietro A, Dumontet C, et al. Recent advances in the discovery of flavonoids and analogs with high-affinity binding to P-glycoprotein responsible for cancer cell multidrug resistance. Med Res Rev 2002;22:512-29
   PubMed Web of Science ®Google Scholar
• Conseil G, Baubichon-Cortay H, Dayan G, et al. Flavonoids: a class of modulators with bifunctional interactions at vicinal ATP- and steroid-binding sites on mouse P-glycoprotein. Proc Natl Acad Sci USA 1998;95:9831-6
   PubMed Web of Science ®Google Scholar
• Zhou S, Lim LY, Chowbay B. Herbal modulation of P-glycoprotein. Drug Metab Rev 2004;36:57-104
   PubMed Web of Science ®Google Scholar
• Kowalski P, Surowiak P, Lage H. Reversal of different drug-resistant phenotypes by an autocatalytic multitarget multiribozyme directed against the transcripts of the ABC transporters MDR1/P-gp, MRP2, and BCRP. Mol Ther 2005;11:508-22
   PubMed Web of Science ®Google Scholar
• Chen T. Overcoming drug resistance by regulating nuclear receptors. Adv Drug Deliv Rev 2010;62:1257-64
   PubMed Web of Science ®Google Scholar
• Synold TW, Dussault I, Forman BM. The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nat Med 2001;7:584-90
   PubMed Web of Science ®Google Scholar
• Thottassery JV, Zambetti GP, Arimori K, et al. p53-dependent regulation of MDR1 gene expression causes selective resistance to chemotherapeutic agents. Proc Natl Acad Sci USA 1997;94:11037-42
   PubMed Web of Science ®Google Scholar
• Sampath J, Sun D, Kidd VJ, et al. Mutant p53 cooperates with ETS and selectively up-regulates human MDR1 not MRP1. J Biol Chem 2001;276:39359-67
   PubMed Web of Science ®Google Scholar
• Sosnik A. Reversal of multidrug resistance by the inhibition of ATP-binding cassette pumps employing “Generally Recognized As Safe” (GRAS) nanopharmaceuticals: a review. Adv Drug Deliv Rev 2013;65:1828-51
   PubMed Web of Science ®Google Scholar
• Riehm H, Biedler JL. Potentiation of drug effect by Tween 80 in Chinese hamster cells resistant to actinomycin D and daunomycin. Cancer Res 1972;32:1195-200
   PubMed Web of Science ®Google Scholar
• Pluchino KM, Hall MD, Goldsborough AS, et al. Collateral sensitivity as a strategy against cancer multidrug resistance. Drug Resist Updat 2012;15:98-105
   PubMed Web of Science ®Google Scholar
• Szakacs G, Annereau JP, Lababidi S, et al. Predicting drug sensitivity and resistance: profiling ABC transporter genes in cancer cells. Cancer Cell 2004;6:129-37
   PubMed Web of Science ®Google Scholar
• Bergman AM, Pinedo HM, Talianidis I, et al. Increased sensitivity to gemcitabine of P-glycoprotein and multidrug resistance-associated protein-overexpressing human cancer cell lines. Br J Cancer 2003;88:1963-70
   PubMed Web of Science ®Google Scholar
• Krzyzanowski D, Bartosz G, Grzelak A. Collateral sensitivity: ABCG2-overexpressing cells are more vulnerable to oxidative stress. Free Radic Biol Med 2014;76:47-52
   PubMed Web of Science ®Google Scholar
• Hall MD, Marshall TS, Kwit AD, et al. Inhibition of glutathione peroxidase mediates the collateral sensitivity of multidrug-resistant cells to tiopronin. J Biol Chem 2014;289:21473-89
   PubMed Web of Science ®Google Scholar
• Broxterman HJ, Pinedo HM, Kuiper CM, et al. Induction by verapamil of a rapid increase in ATP consumption in multidrug-resistant tumor cells. FASEB J 1988;2:2278-82
   PubMed Web of Science ®Google Scholar
• Rao DK, Liu H, Ambudkar SV, et al. A combination of curcumin with either gramicidin or ouabain selectively kills cells that express the multidrug resistance-linked ABCG2 transporter. J Biol Chem 2014;289:31397-410
   PubMed Web of Science ®Google Scholar
• Georges E, Lian J, Laberge R. A tamoxifen derivative, N,N-diethyl-2-[4-(phenylmethyl) phenoxy] ethanamine, selectively targets P-glycoprotein-positive multidrug resistant Chinese hamster cells. Biochem Pharmacol 2014;90:107-14
   PubMed Web of Science ®Google Scholar
• Lorendeau D, Dury L, Genoux-Bastide E, et al. Collateral sensitivity of resistant MRP1-overexpressing cells to flavonoids and derivatives through GSH efflux. Biochem Pharmacol 2014;90:235-45
   PubMed Web of Science ®Google Scholar
• Seo T, Urasaki Y, Takemura H, et al. Arsenic trioxide circumvents multidrug resistance based on different mechanisms in human leukemia cell lines. Anticancer Res 2005;25:991-8
   PubMed Web of Science ®Google Scholar
• Zorov DB, Juhaszova M, Sollott SJ. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev 2014;94:909-50
   PubMed Web of Science ®Google Scholar
• Laberge RM, Ambadipudi R, Georges E. P-glycoprotein mediates the collateral sensitivity of multidrug resistant cells to steroid hormones. Biochem Biophys Res Commun 2014;447:574-9
   PubMed Web of Science ®Google Scholar
• Yu L, Liu S. Autophagy contributes to modulating the cytotoxicities of Bcl-2 homology domain-3 mimetics. Semin Cancer Biol 2013;23:553-60
   PubMed Web of Science ®Google Scholar
• Johnstone RW, Cretney E, Smyth MJ. P-glycoprotein protects leukemia cells against caspase-dependent, but not caspase-independent, cell death. Blood 1999;93:1075-85
   PubMed Web of Science ®Google Scholar
• Ajabnoor GM, Crook T, Coley HM. Paclitaxel resistance is associated with switch from apoptotic to autophagic cell death in MCF-7 breast cancer cells. Cell Death Dis 2012;3:e260
   PubMed Web of Science ®Google Scholar
• Szakacs G, Hall MD, Gottesman MM, et al. Targeting the Achilles heel of multidrug-resistant cancer by exploiting the fitness cost of resistance. Chem Rev 2014;114:5753-74
   PubMed Web of Science ®Google Scholar
• Uboldi S, Bernasconi S, Romano M, et al. Characterization of a new trabectedin-resistant myxoid liposarcoma cell line that shows collateral sensitivity to methylating agents. Int J Cancer 2012;131:59-69
   PubMed Web of Science ®Google Scholar
• Coley HM, Hatzimichael E, Blagden S, et al. Polo Like Kinase 2 Tumour Suppressor and cancer biomarker: new perspectives on drug sensitivity/resistance in ovarian cancer. Oncotarget 2012;3:78-83
   PubMedGoogle Scholar
• Coley HM, Safuwan NA, Chivers P, et al. The cyclin-dependent kinase inhibitor p57(Kip2) is epigenetically regulated in carboplatin resistance and results in collateral sensitivity to the CDK inhibitor seliciclib in ovarian cancer. Br J Cancer 2012;106:482-9
   PubMed Web of Science ®Google Scholar
• Boland MP, Fitzgerald KA, O’Neill LA. Topoisomerase II is required for mitoxantrone to signal nuclear factor kappa B activation in HL60 cells. J Biol Chem 2000;275:25231-8
   PubMed Web of Science ®Google Scholar
• Hermanson DL, Das SG, Li Y, et al. Overexpression of Mcl-1 confers multidrug resistance, whereas topoisomerase IIbeta downregulation introduces mitoxantrone-specific drug resistance in acute myeloid leukemia. Mol Pharmacol 2013;84:236-43
   PubMed Web of Science ®Google Scholar
• Bleeker NP, Cornea RL, Thomas DD, et al. A novel SERCA inhibitor demonstrates synergy with classic SERCA inhibitors and targets multidrug-resistant AML. Mol Pharm 2013;10:4358-66
   PubMedGoogle Scholar
• Das SG, Hermanson DL, Bleeker N, et al. Ethyl 2-amino-6-(3,5-dimethoxyphenyl)-4-(2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (CXL017): a novel scaffold that resensitizes multidrug resistant leukemia cells to chemotherapy. ACS Chem Biol 2013;8:327-35
   PubMed Web of Science ®Google Scholar
• Kuete V, Tchakam PD, Wiench B, et al. Cytotoxicity and modes of action of four naturally occuring benzophenones: 2,2’,5,6’-tetrahydroxybenzophenone, guttiferone E, isogarcinol and isoxanthochymol. Phytomedicine 2013;20:528-36
   PubMed Web of Science ®Google Scholar
• Kuete V, Nkuete AH, Mbaveng AT, et al. Cytotoxicity and modes of action of 4’-hydroxy-2’,6’-dimethoxychalcone and other flavonoids toward drug-sensitive and multidrug-resistant cancer cell lines. Phytomedicine 2014;21:1651-7
   PubMed Web of Science ®Google Scholar
• Imamovic L, Sommer MO. Use of collateral sensitivity networks to design drug cycling protocols that avoid resistance development. Sci Transl Med 2013;5:204ra132
   PubMed Web of Science ®Google Scholar
• Lazar V, Pal Singh G, Spohn R, et al. Bacterial evolution of antibiotic hypersensitivity. Mol Syst Biol 2013;9:700
   PubMed Web of Science ®Google Scholar
• Nakajima K, Isonishi S, Saito M, et al. Characterization of two independent, exposure-time dependent paclitaxel-resistant human ovarian carcinoma cell lines. Hum Cell 2010;23:156-63
   PubMed Web of Science ®Google Scholar
• Kelland LR, Kimbell R, Hardcastle A, et al. Relationships between resistance to cisplatin and antifolates in sensitive and resistant tumour cell lines. Eur J Cancer 1995;31A:981-6
   PubMed Web of Science ®Google Scholar
• Bosanquet AG, Bell PB. Novel ex vivo analysis of nonclassical, pleiotropic drug resistance and collateral sensitivity induced by therapy provides a rationale for treatment strategies in chronic lymphocytic leukemia. Blood 1996;87:1962-71
   PubMed Web of Science ®Google Scholar
• Eichler AF, Chung E, Kodack DP, et al. The biology of brain metastases-translation to new therapies. Nat Rev Clin Oncol 2011;8:344-56
   PubMed Web of Science ®Google Scholar
• Eyal S, Hsiao P, Unadkat JD. Drug interactions at the blood-brain barrier: fact or fantasy? Pharmacol Ther 2009;123:80-104
   PubMed Web of Science ®Google Scholar
• Choo EF, Leake B, Wandel C, et al. Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes. Drug Metab Dispos 2000;28:655-60
   PubMed Web of Science ®Google Scholar
• Kemper EM, van Zandbergen AE, Cleypool C, et al. Increased penetration of paclitaxel into the brain by inhibition of P-Glycoprotein. Clin Cancer Res 2003;9:2849-55
   PubMed Web of Science ®Google Scholar
• Dagenais C, Graff CL, Pollack GM. Variable modulation of opioid brain uptake by P-glycoprotein in mice. Biochem Pharmacol 2004;67:269-76
   PubMed Web of Science ®Google Scholar
• Calatozzolo C, Gelati M, Ciusani E, et al. Expression of drug resistance proteins Pgp, MRP1, MRP3, MRP5 and GST-pi in human glioma. J Neurooncol 2005;74:113-21
   PubMed Web of Science ®Google Scholar
• Dauchy S, Dutheil F, Weaver RJ, et al. ABC transporters, cytochromes P450 and their main transcription factors: expression at the human blood-brain barrier. J Neurochem 2008;107:1518-28
   PubMed Web of Science ®Google Scholar
• Kalvass JC, Polli JW, Bourdet DL, et al. Why clinical modulation of efflux transport at the human blood-brain barrier is unlikely: the ITC evidence-based position. Clin Pharmacol Ther 2013;94:80-94
   PubMed Web of Science ®Google Scholar
• Polli JW, Olson KL, Chism JP, et al. An unexpected synergist role of P-glycoprotein and breast cancer resistance protein on the central nervous system penetration of the tyrosine kinase inhibitor lapatinib (N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino }methyl)-2-furyl]-4-quinazolinamine; GW572016). Drug Metab Dispos 2009;37:439-42
   PubMed Web of Science ®Google Scholar
• Zamek-Gliszczynski MJ, Kalvass JC, Pollack GM, et al. Relationship between drug/metabolite exposure and impairment of excretory transport function. Drug Metab Dispos 2009;37:386-90
   PubMed Web of Science ®Google Scholar
• Agarwal S, Hartz AM, Elmquist WF, et al. Breast cancer resistance protein and P-glycoprotein in brain cancer: two gatekeepers team up. Curr Pharm Des 2011;17:2793-802
   PubMed Web of Science ®Google Scholar
• Burmester GR, Feist E, Dorner T. Emerging cell and cytokine targets in rheumatoid arthritis. Nat Rev Rheumatol 2014;10:77-88
   PubMed Web of Science ®Google Scholar
• Gerlag DM, Haringman JJ, Smeets TJ, et al. Effects of oral prednisolone on biomarkers in synovial tissue and clinical improvement in rheumatoid arthritis. Arthritis Rheum 2004;50:3783-91
   PubMed Web of Science ®Google Scholar
• Hirohata S, Ohshima N, Yanagida T, et al. Regulation of human B cell function by sulfasalazine and its metabolites. Int Immunopharmacol 2002;2:631-40
   PubMed Web of Science ®Google Scholar
• Breedveld FC, Dayer JM. Leflunomide: mode of action in the treatment of rheumatoid arthritis. Ann Rheum Dis 2000;59:841-9
   PubMed Web of Science ®Google Scholar
• Galanaud P, Crevon MC, Dormont J. Effect of azathioprine on in vitro antibody response. Differential effect on B cells involved in thymus-dependent and independent responses. Clin Exp Immunol 1975;22:139-52
   PubMed Web of Science ®Google Scholar
• Li J, Hsu HC, Mountz JD. Managing macrophages in rheumatoid arthritis by reform or removal. Curr Rheumatol Rep 2012;14:445-54
   PubMed Web of Science ®Google Scholar
• Smith MD, Kraan MC, Slavotinek J, et al. Treatment-induced remission in rheumatoid arthritis patients is characterized by a reduction in macrophage content of synovial biopsies. Rheumatology (Oxford) 2001;40:367-74
   PubMed Web of Science ®Google Scholar
• Kobayashi Y, Ueyama S, Arai Y, et al. The active metabolite of leflunomide, A771726, inhibits both the generation of and the bone-resorbing activity of osteoclasts by acting directly on cells of the osteoclast lineage. J Bone Miner Metab 2004;22:318-28
   PubMed Web of Science ®Google Scholar
• Lee CK, Lee EY, Chung SM, et al. Effects of disease-modifying antirheumatic drugs and antiinflammatory cytokines on human osteoclastogenesis through interaction with receptor activator of nuclear factor kappaB, osteoprotegerin, and receptor activator of nuclear factor kappaB ligand. Arthritis Rheum 2004;50:3831-43
   PubMed Web of Science ®Google Scholar
• Kusabe T, Waguri-Nagaya Y, Tanikawa T, et al. The inhibitory effect of disease-modifying anti-rheumatic drugs and steroids on gliostatin/platelet-derived endothelial cell growth factor production in human fibroblast-like synoviocytes. Rheumatol Int 2005;25:625-30
   PubMed Web of Science ®Google Scholar
• Llorente L, Richaud-Patin Y, Diaz-Borjon A, et al. Multidrug resistance-1 (MDR-1) in rheumatic autoimmune disorders. Part I: increased P-glycoprotein activity in lymphocytes from rheumatoid arthritis patients might influence disease outcome. Joint Bone Spine 2000;67:30-9
   PubMed Web of Science ®Google Scholar
• Suzuki K, Saito K, Tsujimura S, et al. Tacrolimus, a calcineurin inhibitor, overcomes treatment unresponsiveness mediated by P-glycoprotein on lymphocytes in refractory rheumatoid arthritis. J Rheumatol 2010;37:512-20
   PubMed Web of Science ®Google Scholar
• Tsujimura S, Saito K, Nakayamada S, et al. Etanercept overcomes P-glycoprotein-induced drug resistance in lymphocytes of patients with intractable rheumatoid arthritis. Mod Rheumatol 2010;20:139-46
   PubMed Web of Science ®Google Scholar
• Tsujimura S, Saito K, Nawata M, et al. Overcoming drug resistance induced by P-glycoprotein on lymphocytes in patients with refractory rheumatoid arthritis. Ann Rheum Dis 2008;67:380-8
   PubMed Web of Science ®Google Scholar
• Borowski LC, Lopes RP, Gonzalez TP, et al. Is steroid resistance related to multidrug resistance-I (MDR-I) in rheumatoid arthritis? Int Immunopharmacol 2007;7:836-44
   PubMed Web of Science ®Google Scholar
• Verbrugge SE, Assaraf YG, Dijkmans BA, et al. Inactivating PSMB5 mutations and P-glycoprotein (multidrug resistance-associated protein/ATP-binding cassette B1) mediate resistance to proteasome inhibitors: ex vivo efficacy of (immuno)proteasome inhibitors in mononuclear blood cells from patients with rheumatoid arthritis. J Pharmacol Exp Ther 2012;341:174-82
   PubMed Web of Science ®Google Scholar
• Pawlik A, Wrzesniewska J, Fiedorowicz-Fabrycy I, et al. The MDR1 3435 polymorphism in patients with rheumatoid arthritis. Int J Clin Pharmacol Ther 2004;42:496-503
   PubMed Web of Science ®Google Scholar
• Drozdzik M, Rudas T, Pawlik A, et al. The effect of 3435C>T MDR1 gene polymorphism on rheumatoid arthritis treatment with disease-modifying antirheumatic drugs. Eur J Clin Pharmacol 2006;62:933-7
   PubMed Web of Science ®Google Scholar
• Chen J, Chen L, Mao N, et al. Association of the MDR1 3435 polymorphism in patients with refractory rheumatoid arthritis in a Chinese population. Rheumatol Int 2012;32:3127-30
   PubMed Web of Science ®Google Scholar
• Takatori R, Takahashi KA, Tokunaga D, et al. ABCB1 C3435T polymorphism influences methotrexate sensitivity in rheumatoid arthritis patients. Clin Exp Rheumatol 2006;24:546-54
   PubMed Web of Science ®Google Scholar
• Kato T, Hamada A, Mori S, et al. Genetic polymorphisms in metabolic and cellular transport pathway of methotrexate impact clinical outcome of methotrexate monotherapy in Japanese patients with rheumatoid arthritis. Drug Metab Pharmacokinet 2012;27:192-9
   PubMed Web of Science ®Google Scholar
• Dickens D, Owen A, Alfirevic A, et al. ABCB1 single nucleotide polymorphisms (1236C>T, 2677G>T, and 3435C>T) do not affect transport activity of human P-glycoprotein. Pharmacogenet Genomics 2013;23:314-23
   PubMed Web of Science ®Google Scholar
• Fung KL, Pan J, Ohnuma S, et al. MDR1 synonymous polymorphisms alter transporter specificity and protein stability in a stable epithelial monolayer. Cancer Res 2014;74:598-608
   PubMed Web of Science ®Google Scholar
• Jamroziak K, Balcerczak E, Smolewski P, et al. MDR1 (ABCB1) gene polymorphism C3435T is associated with P-glycoprotein activity in B-cell chronic lymphocytic leukemia. Pharmacol Rep 2006;58:720-8
   PubMed Web of Science ®Google Scholar
• Ansermot N, Rebsamen M, Chabert J, et al. Influence of ABCB1 gene polymorphisms and P-glycoprotein activity on cyclosporine pharmacokinetics in peripheral blood mononuclear cells in healthy volunteers. Drug Metab Lett 2008;2:76-82
   PubMedGoogle Scholar
• Hider SL, Owen A, Hartkoorn R, et al. Down regulation of multidrug resistance protein-1 expression in patients with early rheumatoid arthritis exposed to methotrexate as a first disease-modifying antirheumatic drug. Ann Rheum Dis 2006;65:1390-3
   PubMed Web of Science ®Google Scholar
• van der Heijden JW, Oerlemans R, Tak PP, et al. Involvement of breast cancer resistance protein expression on rheumatoid arthritis synovial tissue macrophages in resistance to methotrexate and leflunomide. Arthritis Rheum 2009;60:669-77
   PubMed Web of Science ®Google Scholar
• Norris MD, De Graaf D, Haber M, et al. Involvement of MDR1 P-glycoprotein in multifactorial resistance to methotrexate. Int J Cancer 1996;65:613-19
   PubMed Web of Science ®Google Scholar
• Salmon SE, Dalton WS. Relevance of multidrug resistance to rheumatoid arthritis: development of a new therapeutic hypothesis. J Rheumatol Suppl 1996;44:97-101
   PubMedGoogle Scholar
• Honjo K, Takahashi KA, Mazda O, et al. MDR1a/1b gene silencing enhances drug sensitivity in rat fibroblast-like synoviocytes. J Gene Med 2010;12:219-27
   PubMed Web of Science ®Google Scholar
• Kis E, Nagy T, Jani M, et al. Leflunomide and its metabolite A771726 are high affinity substrates of BCRP: implications for drug resistance. Ann Rheum Dis 2009;68:1201-7
   PubMed Web of Science ®Google Scholar
• Diamanti AP, Rosado M, Germano V, et al. Reversion of resistance to immunosuppressive agents in three patients with psoriatic arthritis by cyclosporine A: modulation of P-glycoprotein function. Clin Immunol 2011;138:9-13
   PubMed Web of Science ®Google Scholar
• Hider SL, Hoggard P, Khoo S, et al. Drug efflux transporters in rheumatoid arthritis: comment on the article by Kremer. Arthritis Rheum 2005;52:670; author reply 72
   PubMed Web of Science ®Google Scholar
• Dale J, Alcorn N, Capell H, et al. Combination therapy for rheumatoid arthritis: methotrexate and sulfasalazine together or with other DMARDs. Nat Clin Pract Rheumatol 2007;3:450-8; quiz, following 78
   PubMedGoogle Scholar
• Nozaki Y, Kusuhara H, Kondo T, et al. Species difference in the inhibitory effect of nonsteroidal anti-inflammatory drugs on the uptake of methotrexate by human kidney slices. J Pharmacol Exp Ther 2007;322:1162-70
   PubMed Web of Science ®Google Scholar
• Elsby R, Fox L, Stresser D, et al. In vitro risk assessment of AZD9056 perpetrating a transporter-mediated drug-drug interaction with methotrexate. Eur J Pharm Sci 2011;43:41-9
   PubMed Web of Science ®Google Scholar
• Choo EF, Kurnik D, Muszkat M, et al. Differential in vivo sensitivity to inhibition of P-glycoprotein located in lymphocytes, testes, and the blood-brain barrier. J Pharmacol Exp Ther 2006;317:1012-18
   PubMed Web of Science ®Google Scholar
• Tamaki A, Ierano C, Szakacs G, et al. The controversial role of ABC transporters in clinical oncology. Essays Biochem 2011;50:209-32
   PubMed Web of Science ®Google Scholar
• Yu M, Ocana A, Tannock IF. Reversal of ATP-binding cassette drug transporter activity to modulate chemoresistance: why has it failed to provide clinical benefit? Cancer Metastasis Rev 2013;32:211-27
   PubMed Web of Science ®Google Scholar
• Available from: http://clinicaltrials.gov
   Google Scholar