Advertisement

ABC Transporter-Mediated Multidrug-Resistant Cancer

  • Haneen Amawi
  • Hong-May Sim
  • Amit K. Tiwari
  • Suresh V. Ambudkar
  • Suneet ShuklaEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1141)

Abstract

ATP-binding cassette (ABC) transporters are involved in active pumping of many diverse substrates through the cellular membrane. The transport mediated by these proteins modulates the pharmacokinetics of many drugs and xenobiotics. These transporters are involved in the pathogenesis of several human diseases. The overexpression of certain transporters by cancer cells has been identified as a key factor in the development of resistance to chemotherapeutic agents. In this chapter, the localization of ABC transporters in the human body, their physiological roles, and their roles in the development of multidrug resistance (MDR) are reviewed. Specifically, P-glycoprotein (P-GP), multidrug resistance-associated proteins (MRPs), and breast cancer resistance protein (BCRP/ABCG2) are described in more detail. The potential of ABC transporters as therapeutic targets to overcome MDR and strategies for this purpose are discussed as well as various explanations for the lack of efficacy of ABC drug transporter inhibitors to increase the efficiency of chemotherapy.

Keywords

ABC transporters Multidrug resistance P-glycoprotein Multidrug resistance-associated protein Breast cancer resistance protein 

Notes

Acknowledgments

We thank Dr. Charles R. Ashby, Jr. and George Leiman for their editorial assistance. SVA was supported by the Intramural Research Program of the National Institutes of Health, the National Cancer Institute, and the Center for Cancer Research.

References

  1. Aagrawal M, Garg RJ, Cortes J, Quintas-cardama A (2010) Tyrosine kinase inhibitors: the first decade. Curr Hematol Malig Rep 5:70–80CrossRefGoogle Scholar
  2. Allen JD, van Loevezijn A, Lakhai JM, van Der valk M, van Tellingen O, Reid G et al (2002) Potent and specific inhibition of the breast cancer resistance protein multidrug transporter and in mouse intestine by a novel analogue of fumitremorgin C. Mol Cancer Ther 1:417–425CrossRefGoogle Scholar
  3. Allikmets R, Schriml IM, Hutchinson A, Romano-spica V, Dean M (1998) A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance. Cancer Res 58:5337–5339PubMedGoogle Scholar
  4. Anders MW (1980) Metabolism of drugs by the kidney. Kidney Int 18:636–647CrossRefGoogle Scholar
  5. Anreddy N, Gupta P, Kathawala RJ, Patel A, Wurpel JN, Chen ZS (2014) Tyrosine kinase inhibitors as reversal agents for ABC transporter mediated drug resistance. Molecules 19:13848–13877CrossRefPubMedPubMedCentralGoogle Scholar
  6. Arceci RJ (1993) Clinical significance of P-glycoprotein in multidrug resistance malignancies. Blood 81:2215–2222PubMedGoogle Scholar
  7. Arora A, Scholar E (2005) Role of Tyrosine Kinase Inhibitors in cancer therapy. J Pharmacol Exp Ther 315:971–986CrossRefGoogle Scholar
  8. Bao I, Hazari S, Mehra S, Kaushal D, Moroz Km Dash S (2012) Increased expression of p-glycoprotein and doxorubicin chemoresistance of metastatic breast cancer is regulated by miR-298. Am J Pathol 180:2490–2503CrossRefPubMedPubMedCentralGoogle Scholar
  9. Baselga J, Swain SM (2009) Novel anticancer targets: revisiting ERBB2 and discovering ERBB3. Nat Rev Cancer 9:463–475CrossRefGoogle Scholar
  10. Begicevic RR, Falasca M (2017) ABC transporters in cancer stem cells: beyond chemoresistance. Int J Mol Sci 18:2362CrossRefPubMedPubMedCentralGoogle Scholar
  11. Binyamin I, Assaraf YG, Hhaus-cohen M, Stark M, Reiter Y (2004) Targeting an extracellular epitope of the human multidrug resistance protein 1 (MRP1) in malignant cells with a novel recombinant single chain Fv antibody. Int J Cancer 110:882–890CrossRefGoogle Scholar
  12. Borowski E, Bontemps-gracz MM, Piwkowska A (2005) Strategies for overcoming ABC-transporters-mediated multidrug resistance (MDR) of tumor cells. Acta Biochim Pol 52:609–627PubMedGoogle Scholar
  13. Borst P, Evers R, Kool M, Wijnholds J (2000) A family of drug transporters: the multidrug resistance-associated proteins. J Natl Cancer Inst 92:1295–1302CrossRefGoogle Scholar
  14. Bose SJ, Scott-Ward TS, Cai Z, Sheppard DN (2015) Exploiting species differences to understand the CFTR Cl- channel. Biochem Soc Trans 43:975–982CrossRefGoogle Scholar
  15. Brandt C, Bethmann K, Gastens AM, Loscher W (2006) The multidrug transporter hypothesis of drug resistance in epilepsy: proof-of-principle in a rat model of temporal lobe epilepsy. Neurobiol Dis 24:202–211CrossRefPubMedPubMedCentralGoogle Scholar
  16. Breedveld P, Beijnen JH, Schellens JHM (2006) Use of P-glycoprotein and BCRP inhibitors to improve oral bioavailability and CNS penetration of anticancer drugs. Trends Pharmacol Sci 27:17–24CrossRefGoogle Scholar
  17. Brendel C, Scharenberg C, Dohse M, Robey RW, Bates SE, Shukla S et al (2007) Imatinib mesylate and nilotinib (AMN107) exhibit high-affinity interaction with ABCG2 on primitive hematopoietic stem cells. Leukemia 21:1267–1275CrossRefGoogle Scholar
  18. Brooks-wilson A, Marcil M, Clee SM, Zhang LH, Roomp K, van Dam M et al (1999) Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat Genet 22:336–345CrossRefGoogle Scholar
  19. Brozik A, Hegedus C, Erdei Z, Hegedus T, Ozvegy-laczka C, Szakacs G et al (2011) Tyrosine kinase inhibitors as modulators of ATP binding cassette multidrug transporters: substrates, chemosensitizers or inducers of acquired multidrug resistance? Expert Opin Drug Metab Toxicol 7:623–642CrossRefGoogle Scholar
  20. Bugde P, Biswas R, Merien F, Lu J, Liu DX, Chen M et al (2017) The therapeutic potential of targeting ABC transporters to combat multi-drug resistance. Expert Opin Ther Targets 21:511–530CrossRefGoogle Scholar
  21. Busse D, Yakes FM, Lenferink AE, Arteaga C (2001) Tyrosine kinase inhibitors: rationale, mechanisms of action, and implications for drug resistance. Semin Oncol 28:47–55CrossRefGoogle Scholar
  22. Cai SX (2007) Small molecule vascular disrupting agents: potential new drugs for cancer treatment. Recent Pat Anticancer Drug Discov 2:79–101CrossRefGoogle Scholar
  23. Cai L, Fisher AL, Huang H, Xie Z (2016) CRISPR-mediated genome editing and human diseases. Genes Dis 3:244–251CrossRefPubMedPubMedCentralGoogle Scholar
  24. Campbell M, Humphries P (2012) The blood-retina barrier: tight junctions and barrier modulation. Adv Exp Med Biol 763:70–84CrossRefGoogle Scholar
  25. Cao D, Qin S, Mu Y, Zhong M (2017) The role of MRP1 in the multidrug resistance of colorectal cancer. Oncol Lett 13:2471–2476CrossRefPubMedPubMedCentralGoogle Scholar
  26. Chan LM, Lowes S, Hirst BH (2004) The ABCs of drug transport in intestine and liver: efflux proteins limiting drug absorption and bioavailability. Eur J Pharm Sci 21:25–51CrossRefGoogle Scholar
  27. Chang G (2003) Multidrug resistance ABC transporters. FEBS Lett 555:102–105CrossRefGoogle Scholar
  28. Chen YF, Fu LW (2011) Mechanisms of acquired resistance to tyrosine kinase inhibitors. Acta Pharm Sin B 1:197–207CrossRefGoogle Scholar
  29. Chen ZS, Tiwari AK (2011) Multidrug resistance proteins (MRPs/ABCCs) in cancer chemotherapy and genetic diseases. FEBS J 278:3226–3245CrossRefPubMedPubMedCentralGoogle Scholar
  30. Chen AM, Zhang M, Wei D, Stueber D, Taratula O, Minko T et al (2009) Co-delivery of doxorubicin and Bcl-2 siRNA by mesoporous silica nanoparticles enhances the efficacy of chemotherapy in multidrug-resistant cancer cells. Small 5:2673–2677CrossRefPubMedPubMedCentralGoogle Scholar
  31. Choi CH (2005) ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal. Cancer Cell Int 5:30CrossRefPubMedPubMedCentralGoogle Scholar
  32. Choi YH, Yu AM (2014) ABC transporters in multidrug resistance and pharmacokinetics, and strategies for drug development. Curr Pharm Des 20:793–807CrossRefPubMedPubMedCentralGoogle Scholar
  33. Choo EF, Leake B, Wandel C, Imamura H, Wood A, Wilkinson GR et al (2000) Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes. Drug Metab Dispos 28:655–560PubMedGoogle Scholar
  34. Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KV et al (1992) Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science 258:1650–1654CrossRefGoogle Scholar
  35. Coley HM (2010) Overcoming multidrug resistance in cancer: clinical studies of p-glycoprotein inhibitors. Methods Mol Biol 596:341–358CrossRefGoogle Scholar
  36. Conseil G, Perez-victoria JM, Jault JM, Gamarro F, Goffeau A, Hofmann J et al (2001) Protein kinase C effectors bind to multidrug ABC transporters and inhibit their activity. Biochemistry 40:2564–2571CrossRefGoogle Scholar
  37. Cooray HC, Blackmore CG, Maskell L, Barrand MA (2002) Localisation of breast cancer resistance protein in microvessel endothelium of human brain. Neuroreport 13:2059–2063CrossRefPubMedPubMedCentralGoogle Scholar
  38. Cort A, Ozben T (2015) Natural product modulators to overcome multidrug resistance in cancer. Nutr Cancer 67:411–423CrossRefGoogle Scholar
  39. Cortes JE, Kim DW, Kantarjian HM, Brummendorf TH, Dyagil I, Griskevicius L et al (2012) Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial. J Clin Oncol 30:3486–3492CrossRefPubMedPubMedCentralGoogle Scholar
  40. Cripe LD, Uno H, Paietta EM, Litzow MR, Ketterling RP, Bennett JM et al (2010) Zosuquidar, a novel modulator of P-glycoprotein, does not improve the outcome of older patients with newly diagnosed acute myeloid leukemia: a randomized, placebo-controlled trial of the Eastern Cooperative Oncology Group 3999. Blood 116:4077–4085CrossRefPubMedPubMedCentralGoogle Scholar
  41. Dai CL, Liang YJ, Wang YS, Tiwari AK, Yan YY, Wang F et al (2009) Sensitization of ABCG2-overexpressing cells to conventional chemotherapeutic agent by sunitinib was associated with inhibiting the function of ABCG2. Cancer Lett 279:74–83CrossRefGoogle Scholar
  42. Dano K (1973) Active outward transport of daunomycin in resistant Ehrlich ascites tumor cells. Biochim Biophys Acta 323:466–483CrossRefGoogle Scholar
  43. Dantzig AH, Shepard RL, Cao J, Law KL, Ehlhardt WJ, Baughman TM et al (1996) Reversal of P-glycoprotein-mediated multidrug resistance by a potent cyclopropyldibenzosuberane modulator, LY335979. Cancer Res 56:4171–4179PubMedPubMedCentralGoogle Scholar
  44. Dantzig AH, Shepard RL, Law KL, Tabas L, Pratt S, Gillespie JS et al (1999) Selectivity of the multidrug resistance modulator, LY335979, for P-glycoprotein and effect on cytochrome P-450 activities. J Pharmacol Exp Ther 290:854–862PubMedPubMedCentralGoogle Scholar
  45. Daood MJ, Tsai C, Ahdab-barmada M, Watchko JF (2008) ABC transporter (P-GP/ABCB1, MRP1/ABCC1, BCRP/ABCG2) expression in the developing human CNS. Neuropediatrics 39:211CrossRefGoogle Scholar
  46. Darmostuk M, Rimpelova S, Gbelcova H, Ruml T (2015) Current approaches in SELEX: an update to aptamer selection technology. Biotechnol Adv 33:1141–1161CrossRefGoogle Scholar
  47. Dean M, Allikmets R (1995) Evolution of ATP-binding cassette transporter genes. Curr Opin Genet Dev 5:779–785CrossRefGoogle Scholar
  48. Dean M, Hamon Y, Chimini G (2001) The human ATP-binding cassette (ABC) transporter superfamily. J Lipid Res 42:1007–1017Google Scholar
  49. Deng J, Shao J, Markowitz JS, An G (2014) ABC transporters in multi-drug resistance and ADME-Tox of small molecule tyrosine kinase inhibitors. Pharm Res 31:2237–2255CrossRefGoogle Scholar
  50. Depeille P, Cuq P, Passagne I, Evrard A, Vian L (2005) Combined effects of GSTP1 and MRP1 in melanoma drug resistance. Br J Cancer 93:216–223CrossRefPubMedPubMedCentralGoogle Scholar
  51. Dezi M, Fribourg PF, Di Cicco A, Arnaud O, Marco S, Falson P et al (2010) The multidrug resistance half-transporter ABCG2 is purified as a tetramer upon selective extraction from membranes. Biochim Biophys Acta 1798:2094–2101CrossRefGoogle Scholar
  52. Díaz-coránguez M, Ramos C, Antonetti DA (2017) The inner blood-retinal barrier: cellular basis and development. Vis Res 139:123–137CrossRefGoogle Scholar
  53. Doyle LA, Yang W, Abruzzo LV, Krogmann T, Gao Y, Rishi AK et al (1998) A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci U S A 95:15665–15670CrossRefPubMedPubMedCentralGoogle Scholar
  54. Drion N, Lemaire M, Lefauconnier JM, Scherrmann JM (1996) Role of P-glycoprotein in the blood-brain transport of colchicine and vinblastine. J Neurochem 67:1688–1693CrossRefGoogle Scholar
  55. Efferth T, Futscher BW, Osieka R (2001) 5-Azacytidine modulates the response of sensitive and multidrug-resistant K562 leukemic cells to cytostatic drugs. Blood Cells Mol Dis 27:637–648CrossRefGoogle Scholar
  56. Elali A, Hermann DM (2012) Liver X receptor activation enhances blood-brain barrier integrity in the ischemic brain and increases the abundance of ATP-binding cassette transporters ABCB1 and ABCC1 on brain capillary cells. Brain Pathol 22:175–187CrossRefGoogle Scholar
  57. Flaherty KT, Puzanov I, Kim KB, Ribas A, Mcarthur GA, Sosman JA et al (2010) Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 363:809–819CrossRefPubMedPubMedCentralGoogle Scholar
  58. Fox E, Bates SE (2007) Tariquidar (XR9576): a P-glycoprotein drug efflux pump inhibitor. Expert Rev Anticancer Ther 7:447–459CrossRefGoogle Scholar
  59. Gandhi NS, Tekade RK, Chougule MB (2014) Nanocarrier mediated delivery of siRNA/miRNA in combination with chemotherapeutic agents for cancer therapy: current progress and advances. J Control Release 94:238–256CrossRefGoogle Scholar
  60. Ganju A, Yallapu MM, Khan S, Behrman SW, Chauhan SC, Jaggi M (2014) Nanoways to overcome docetaxel resistance in prostate cancer. Drug Resist Updat 17:13–23CrossRefPubMedPubMedCentralGoogle Scholar
  61. Gilbert LA, Larson MH, Morsut L, Liu Z, Brar GA, Torres SE et al (2013) CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 154:442–451CrossRefPubMedPubMedCentralGoogle Scholar
  62. Goler-baron V, Assaraf YG (2012) Overcoming multidrug resistance via photodestruction of ABCG2-rich extracellular vesicles sequestering photosensitive chemotherapeutics. PLoS One 7:e35487CrossRefPubMedPubMedCentralGoogle Scholar
  63. Gotink KJ, Verheul HM (2010) Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism of action? Angiogenesis 13:1–14CrossRefGoogle Scholar
  64. Greenberg PL, Lee SJ, Advani R, Tallman M, Sikic BI, Letendre L et al (2004) Mitoxantrone, etoposide, and cytarabine with or without valspodar in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome: a phase III trial (E2995). J Clin Oncol 22:1078–1086CrossRefPubMedPubMedCentralGoogle Scholar
  65. Guay SP, Brisson D, Munger J, Lamarche B, Gaudet D, Bouchard L (2012) ABCA1 gene promoter DNA methylation is associated with HDL particle profile and coronary artery disease in familial hypercholesterolemia. Epigenetics 7:464–472CrossRefGoogle Scholar
  66. Guo S, Lv L, Yuanyuan Shen Y, Hu Z, He Q, Chen X (2016) A nanoparticulate pre-chemosensitizer for efficacious chemotherapy of multidrug resistant breast cancer. Scientific Reports 6:21459Google Scholar
  67. Guo X, To KKW, Chen Z, Wang X, Zhang J, Luo M et al (2018) Dacomitinib potentiates the efficacy of conventional chemotherapeutic agents via inhibiting the drug efflux function of ABCG2 in vitro and in vivo. J Exp Clin Cancer Res 37:31CrossRefPubMedPubMedCentralGoogle Scholar
  68. Ha JS, Byun J, Ahn DR (2016) Overcoming doxorubicin resistance of cancer cells by Cas9-mediated gene disruption. Sci Rep 6:22847CrossRefPubMedPubMedCentralGoogle Scholar
  69. Hartmann JT, Haap M, Kopp HG, Lipp HP (2009) Tyrosine kinase inhibitors – a review on pharmacology, metabolism and side effects. Curr Drug Metab 10:470–481CrossRefGoogle Scholar
  70. Hasanabady MH, Kalalinia F (2016) ABCG2 inhibition as a therapeutic approach for overcoming multidrug resistance in cancer. J Biosci 41:313–324CrossRefGoogle Scholar
  71. Hauser IA, Schaeffeler E, Gauer S, Scheuermann EH, Wegner B, Gossmann J et al (2005) ABCB1 genotype of the donor but not of the recipient is a major risk factor for cyclosporine-related nephrotoxicity after renal transplantation. J Am Soc Nephrol 16:1501–1511CrossRefGoogle Scholar
  72. Hlavata I, Mohelnikova-duchonova B, Vaclavikova R, Liska V, Pitule P, Novak P et al (2012) The role of ABC transporters in progression and clinical outcome of colorectal cancer. Mutagenesis 27:187–196CrossRefGoogle Scholar
  73. Hong L, Han Y, Zhang H, Li M, Gong T, Sun L, Wu K, Zhao Q, Fan D (2010) The prognostic and chemotherapeutic value of miR-296 in esophageal squamous cell carcinoma. Ann Surg 251:1056–1063CrossRefGoogle Scholar
  74. Hughes CS, Vaden SL, Manaugh CA, Price GS, Hudson LC (1998) Modulation of doxorubicin concentration by cyclosporin A in brain and testicular barrier tissues expressing P-glycoprotein in rats. J Neuro-Oncol 37:45–54CrossRefGoogle Scholar
  75. Huls M, Brown CD, Windass AS, Sayer R, van Den heuvel JJ, Heemskerk S et al (2008) The breast cancer resistance protein transporter ABCG2 is expressed in the human kidney proximal tubule apical membrane. Kidney Int 73:220–225CrossRefGoogle Scholar
  76. Ifergan I, Shafran A, Jansen G, Hooijberg JH, Scheffer GL, Assaraf YG (2004) Folate deprivation results in the loss of breast cancer resistance protein (BCRP/ABCG2) expression. A role for BCRP in cellular folate homeostasis. J Biol Chem 279:25527–25534CrossRefGoogle Scholar
  77. Ito K, Nguyen HT, Kato Y, Wakayama T, Kubo Y, Iseki S et al (2008) P-Glycoprotein (Abcb1) is involved in absorptive drug transport in skin. J Control Release 131:198–204CrossRefGoogle Scholar
  78. Jabbour E, Kantarjian HM, Saglio G, Steegmann JL, Shah NP, Boque C et al (2014) Early response with dasatinib or imatinib in chronic myeloid leukemia: 3-year follow-up from a randomized phase 3 trial (DASISION). Blood 123:494–500CrossRefPubMedPubMedCentralGoogle Scholar
  79. Jin X, Zhou B, Xue L, San W (2015) Soluplus® micelles as a potential drug delivery system for reversal of resistant tumor. Biomed Pharmacother 69:388–395CrossRefGoogle Scholar
  80. Johnatty SE, Beesley J, Paul J, Fereday S, Spurdle AB, Webb PM et al (2008) ABCB1 (MDR 1) polymorphisms and progression-free survival among women with ovarian cancer following paclitaxel/carboplatin chemotherapy. Clin Cancer Res 14:5594–5601CrossRefGoogle Scholar
  81. Jonker JW, Smit JW, Brinkhuis RF, Maliepaard M, Beijnen JH, Schellens JH et al (2000) Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. J Natl Cancer Inst 92:1651–1656CrossRefGoogle Scholar
  82. Joshi AA, Vaidya SS, St-Pierre MV, Mikheev AM, Desino KE, Nyandege AN et al (2016) Placental ABC transporters: biological impact and pharmaceutical significance. Pharm Res 33:2847–2878CrossRefPubMedPubMedCentralGoogle Scholar
  83. Juliano RL, Ling V (1976) A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 455:152–162CrossRefGoogle Scholar
  84. Kannan P, Telu S, Shukla S, Ambudkar SV, Pike VW, Halldin C et al (2011) The “specific” P-glycoprotein inhibitor tariquidar is also a substrate and an inhibitor for breast cancer resistance protein (BCRP/ABCG2). ACS Chem Neurosci 2:82–89CrossRefGoogle Scholar
  85. Kapse-Mistry S, Govender T, Srivastava R, Yergeri M (2014) Nanodrug delivery in reversing multidrug resistance in cancer cells. Front Pharmacol 5:159PubMedPubMedCentralGoogle Scholar
  86. Karthikeyan S, Hoti SL (2015) Development of fourth generation ABC inhibitors from natural products: a novel approach to overcome cancer multidrug resistance. Anti Cancer Agents Med Chem 15:605–615CrossRefGoogle Scholar
  87. Keller RP, Altermatt HJ, Nooter K, Poschmann G, Laissue JA, Bollinger P et al (1992) SDZ PSC 833, a non-immunosuppressive cyclosporine: its potency in overcoming P-glycoprotein-mediated multidrug resistance of murine leukemia. Int J Cancer 50:593–597CrossRefGoogle Scholar
  88. Kemper EM, van Zandbergen AE, Cleypool C, Mos HA, Boogerd W, Beijnen JH et al (2003) Increased penetration of paclitaxel into the brain by inhibition of P-Glycoprotein. Clin Cancer Res 9:2849–2855PubMedPubMedCentralGoogle Scholar
  89. Kemper EM, Cleypool C, Boogerd W, Beijnen JH, van Tellingen O (2004) The influence of the P-glycoprotein inhibitor zosuquidar trihydrochloride (LY335979) on the brain penetration of paclitaxel in mice. Cancer Chemother Pharmacol 53:173–178CrossRefPubMedPubMedCentralGoogle Scholar
  90. Kielar D, Kaminski WE, Liebisch G, Piehler A, Wenzel JJ, Möhle C et al (2003) Adenosine triphosphate binding cassette (ABC) transporters are expressed and regulated during terminal keratinocyte differentiation: a potential role for abca7 in epidermal lipid reorganization. J Invest Dermatol 121:465–474CrossRefGoogle Scholar
  91. Krishnamurthy P, Ross DD, Nakanishi T, Bailey-Dell K, Zhou S, Mercer KE et al (2004) The stem cell marker Bcrp/ABCG2 enhances hypoxic cell survival through interactions with heme. J Biol Chem 279:24218–24225CrossRefGoogle Scholar
  92. Kruh GD, Zeng H, Rea PA, Liu G, Chen ZS, Lee K et al (2001) MRP subfamily transporters and resistance to anticancer agents. J Bioenerg Biomembr 33:493–501CrossRefGoogle Scholar
  93. Kruhn A, Wang A, Fruehauf JH, Lage H (2009) Delivery of short hairpin RNAs by transkingdom RNA interference modulates the classical ABCB1-mediated multidrug-resistant phenotype of cancer cells. Cell Cycle 8:3349–3354CrossRefGoogle Scholar
  94. Kruijtzer CM, Beijnen JH, Rosing H, Ten Bokkel Huinink WW, Schot M, Jewell RC et al (2002) Increased oral bioavailability of topotecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918. J Clin Oncol 20:2943–2950CrossRefGoogle Scholar
  95. Kuang Y, Shen T, Chen X, Sodani K, Hopper-Borge E, Tiwari AK et al (2010) Lapatinib and erlotinib are potent reversal agents for MRP7 (ABCC10)-mediated multidrug resistance. Biochem Pharmacol 79:154–161CrossRefGoogle Scholar
  96. Kuppens IE, Witteveen EO, Jewell RC, Radema SA, Paul EM, Mangum SG et al (2007) A phase I, randomized, open-label, parallel-cohort, dose-finding study of elacridar (GF120918) and oral topotecan in cancer patients. Clin Cancer Res 13:3276–3285CrossRefGoogle Scholar
  97. Lage H (2016) Gene therapeutic approaches to overcome ABCB1-mediated drug resistance. Recent Results Cancer Res 209:87–94CrossRefGoogle Scholar
  98. Lage H, Kruhn A (2010) Bacterial delivery of RNAi effectors: transkingdom RNAi. J Vis Exp 42:pii: 2099Google Scholar
  99. Lai Y, Gallo RL (2009) AMPed Up immunity: how antimicrobial peptides have multiple roles in immune defense. Trends Immunol 30:131–141CrossRefPubMedPubMedCentralGoogle Scholar
  100. Larson RA, Hochhaus A, Hughes TP, Clark RE, Etienne G, Kim DW et al (2012) Nilotinib vs imatinib in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTnd 3-year follow-up. Leukemia 26:2197–2203CrossRefGoogle Scholar
  101. Lawn RM, Wade DP, Garvin MR, Wang X, Schwartz K, Porter JG et al (1999) The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway. J Clin Invest 104:R25–R31CrossRefPubMedPubMedCentralGoogle Scholar
  102. Lehne G (2000) P-glycoprotein as a drug target in the treatment of multidrug resistant cancer. Curr Drug Targets 1:85–99CrossRefGoogle Scholar
  103. Lhomme C, Joly F, Walker JL, Lissoni AA, Nicoletto MO, Manikhas GM et al (2008) Phase III study of valspodar (PSC 833) combined with paclitaxel and carboplatin compared with paclitaxel and carboplatin alone in patients with stage IV or suboptimally debulked stage III epithelial ovarian cancer or primary peritoneal cancer. J Clin Oncol 26:2674–2682CrossRefGoogle Scholar
  104. Li L, Shukla S, Lee A, Garfield SH, Maloney DJ, Ambudkar SV et al (2010) The skin cancer chemotherapeutic agent ingenol-3-angelate (PEP005) is a substrate for the epidermal multidrug transporter (ABCB1) and targets tumor vasculature. Cancer Res 70:4509–4519CrossRefPubMedPubMedCentralGoogle Scholar
  105. Li H, Karl T, Garner B (2015) Understanding the function of ABCA7 in Alzheimer’s disease. Biochem Soc Trans 43:920–923CrossRefPubMedPubMedCentralGoogle Scholar
  106. Li W, Zhang H, Assaraf YG, Zhao K, Xu X, Xie J et al (2016) Overcoming ABC transporter-mediated multidrug resistance: molecular mechanisms and novel therapeutic drug strategies. Drug Resist Updat 27:14–29CrossRefGoogle Scholar
  107. Li J, Kumar P, Anreddy N, Zhang YK, Wang YJ, Chen Y et al (2017) Quizartinib (AC220) reverses ABCG2-mediated multidrug resistance: in vitro and in vivo studies. Oncotarget 8:93785–93799PubMedPubMedCentralGoogle Scholar
  108. Li H, Krstin S, Wang S, Wink M (2018) Capsaicin and piperine can overcome multidrug resistance in cancer cells to doxorubicin. Molecules 23:pii: E557CrossRefGoogle Scholar
  109. Linton KJ (2007) Structure and function of ABC transporters. Physiology (Bethesda) 22:122–130Google Scholar
  110. Linton KJ, Holland IB (2011) The ABC transporters of human physiology and disease: genetics and biochemistry of ATP binding cassette transporters, 1st edn. World Scientific Publishing Company, HackensackCrossRefGoogle Scholar
  111. Long S, Sousa E, Kijjoa A, Pinto MM (2016) Marine natural products as models to circumvent multidrug resistance. Molecules 21:892CrossRefPubMedPubMedCentralGoogle Scholar
  112. Loscher W, Potschka H (2002) Role of multidrug transporters in pharmacoresistance to antiepileptic drugs. J Pharmacol Exp Ther 301:7–14CrossRefGoogle Scholar
  113. Löscher W, POTSCHKA H (2005) Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx 2:86–98CrossRefPubMedPubMedCentralGoogle Scholar
  114. Loscher W, Luna-Tortos C, Romermann K, Fedrowitz M (2011) Do ATP-binding cassette transporters cause pharmacoresistance in epilepsy? Problems and approaches in determining which antiepileptic drugs are affected. Curr Pharm Des 17:2808–2828CrossRefGoogle Scholar
  115. Maliepaard M, van Gastelen MA, Tohgo A, Hausheer FH, Van Waardenburg RC, De Jong LA et al (2001) Circumvention of breast cancer resistance protein (BCRP)-mediated resistance to camptothecins in vitro using non-substrate drugs or the BCRP inhibitor GF120918. Clin Cancer Res 7:935–941PubMedGoogle Scholar
  116. Manoochehri S, Darvishi B, Kamalinia G, Amini M, Fallah M, Ostad SN et al (2013) Surface modification of PLGA nanoparticles via human serum albumin conjugation for controlled delivery of docetaxel. Daru 21:58CrossRefPubMedPubMedCentralGoogle Scholar
  117. Mao Q, Unadkat JD (2015) Role of the breast cancer resistance protein (BCRP/ABCG2) in drug transport—an update. AAPS J 17:65–82CrossRefGoogle Scholar
  118. Marcil M, Brooks-Wilson A, Clee SM, Roomp K, Zhang LH, Yu L et al (1999) Mutations in the ABC1 gene in familial HDL deficiency with defective cholesterol efflux. Lancet 354:1341–1346CrossRefGoogle Scholar
  119. Marquez B, van Bambeke F (2011) ABC multidrug transporters: target for modulation of drug pharmacokinetics and drug-drug interactions. Curr Drug Targets 12:600–620CrossRefGoogle Scholar
  120. Martin C, Berridge G, Mistry P, Higgins C, Charlton P, Callaghan R (1999) The molecular interaction of the high affinity reversal agent XR9576 with P-glycoprotein. Br J Pharmacol 128:403–411CrossRefPubMedPubMedCentralGoogle Scholar
  121. Masereeuw R, Russel FG (2010) Therapeutic implications of renal anionic drug transporters. Pharmacol Ther 126:200–216CrossRefGoogle Scholar
  122. Masereeuw R, Russel FGM (2012) Regulatory pathways for atp-binding cassette transport proteins in kidney proximal tubules. AAPS J 14:883–894CrossRefPubMedPubMedCentralGoogle Scholar
  123. Mechetner EB, Roninson IB (1992) Efficient inhibition of P-glycoprotein-mediated multidrug resistance with a monoclonal antibody. Proc Natl Acad Sci U S A 89:5824–5828CrossRefPubMedPubMedCentralGoogle Scholar
  124. Mi YJ, Liang YJ, Huang HB, Zhao HY, Wu CP, Wang F et al (2010) Apatinib (YN968D1) reverses multidrug resistance by inhibiting the efflux function of multiple ATP-binding cassette transporters. Cancer Res 70:7981–7991CrossRefPubMedPubMedCentralGoogle Scholar
  125. Miller DS (2015) Regulation of ABC transporters at the blood-brain barrier. Clin Pharmacol Ther 97:395–403CrossRefPubMedPubMedCentralGoogle Scholar
  126. Miyake K, Mickley L, Litman T, Zhan Z, Robey R, Cristensen B et al (1999) Molecular cloning of cDNAs which are highly overexpressed in mitoxantrone-resistant cells: demonstration of homology to ABC transport genes. Cancer Res 59:8–13PubMedGoogle Scholar
  127. Moe AJ (1995) Placental amino acid transport. Am J Phys 268:C1321–C1331CrossRefGoogle Scholar
  128. Mohelnikova-Duchonova B, Brynychova V, Oliverius M, Honsova E, Kala Z, Muckova K et al (2013) Differences in transcript levels of ABC transporters between pancreatic adenocarcinoma and nonneoplastic tissues. Pancreas 42:707–716CrossRefGoogle Scholar
  129. Molday RS, Zhong M, Quazi F (2009) The role of the photoreceptor ABC transporter ABCA4 in lipid transport and Stargardt macular degeneration. Biochim Biophys Acta 1791:573–583CrossRefPubMedPubMedCentralGoogle Scholar
  130. Morschhauser F, Zinzani PL, Burgess M, Sloots L, Bouafia F, Dumontet C (2007) Phase I/II trial of a P-glycoprotein inhibitor, Zosuquidar.3HCl trihydrochloride (LY335979), given orally in combination with the CHOP regimen in patients with non-Hodgkin’s lymphoma. Leuk Lymphoma 48:708–715CrossRefGoogle Scholar
  131. Naito M, Tsuge H, Kuroko C, Koyama T, Tomida A, Tatsuta T et al (1993) Enhancement of cellular accumulation of cyclosporine by anti-P-glycoprotein monoclonal antibody MRK-16 and synergistic modulation of multidrug resistance. J Natl Cancer Inst 85:311–316CrossRefGoogle Scholar
  132. Nicolaou M, Andress EJ, Zolnerciks JK, Dixon PH, Williamson C, Linton KJ (2012) Canalicular ABC transporters and liver disease. J Pathol 226:300–315CrossRefPubMedPubMedCentralGoogle Scholar
  133. Nies AT, Konig J, Pfannschmidt M, Klar E, Hofmann WJ, Keppler D (2001) Expression of the multidrug resistance proteins MRP2 and MRP3 in human hepatocellular carcinoma. Int J Cancer 94:492–499CrossRefGoogle Scholar
  134. Nobili S, Landini I, Giglioni B, Mini E (2006) Pharmacological strategies for overcoming multidrug resistance. Curr Drug Targets 7:861–879CrossRefGoogle Scholar
  135. Norouzi-Barough L, Sarookhani M, Salehi R, Sharifi M, Moghbelinejad S (2018) CRISPR/Cas9, a new approach to successful knockdown of ABCB1/P-glycoprotein and reversal of chemosensitivity in human epithelial ovarian cancer cell line. Iran J Basic Med Sci 21:181–187PubMedPubMedCentralGoogle Scholar
  136. Osman-Ponchet H, Boulai A, Kouidhi M, Sevin K, Alriquet M, Gaborit A et al (2014) Characterization of ABC transporters in human skin. Drug Metabol Drug Interact 29:91–100CrossRefGoogle Scholar
  137. Ozvegy-Laczka C, Hegedus T, Varady G, Ujhelly O, Schuetz JD, Varadi A et al (2004) High-affinity interaction of tyrosine kinase inhibitors with the ABCG2 multidrug transporter. Mol Pharmacol 65:1485–1895CrossRefGoogle Scholar
  138. Palmeira A, Sousa E, Vasconcelos MH, Pinto MM (2012) Three decades of P-GP inhibitors: skimming through several generations and scaffolds. Curr Med Chem 19:1946–2025CrossRefGoogle Scholar
  139. Paul MK, Mukhopadhyay AK (2004) Tyrosine kinase – role and significance in cancer. Int J Med Sci 1:101–115CrossRefPubMedPubMedCentralGoogle Scholar
  140. Peca D, Cutrera R, Masotti A, Boldrini R, Danhaive O (2015) ABCA3, a key player in neonatal respiratory transition and genetic disorders of the surfactant system. Biochem Soc Trans 43:913–919CrossRefGoogle Scholar
  141. Pollock NL, Rimington TL, Ford RC (2015) Characterizing diverse orthologues of the cystic fibrosis transmembrane conductance regulator protein for structural studies. Biochem Soc Trans 43:894–900CrossRefGoogle Scholar
  142. Potschka H, Luna-Munguia H (2014) CNS transporters and drug delivery in epilepsy. Curr Pharm Des 20:1534–1542CrossRefGoogle Scholar
  143. Potschka H, Fedrowitz M, Loscher W (2002) P-Glycoprotein-mediated efflux of phenobarbital, lamotrigine, and felbamate at the blood-brain barrier: evidence from microdialysis experiments in rats. Neurosci Lett 327:173–176CrossRefGoogle Scholar
  144. Qiu L, Chen T, Ocsoy I, Yasun E, Wu C, Zhu G et al (2015) A cell-targeted, size-photocontrollable, nuclear-uptake nanodrug delivery system for drug-resistant cancer therapy. Nano Lett 15:457–463CrossRefGoogle Scholar
  145. Rabindran SK, Ross DD, Doyle LA, Yang W, Greenberger LM (2000) Fumitremorgin C reverses multidrug resistance in cells transfected with the breast cancer resistance protein. Cancer Res 60:47–50PubMedGoogle Scholar
  146. Robey RW, Shukla S, Steadman K, Obrzut T, Finley EM, Ambudkar SV et al (2007) Inhibition of ABCG2-mediated transport by protein kinase inhibitors with a bisindolylmaleimide or indolocarbazole structure. Mol Cancer Ther 6:1877–1885CrossRefGoogle Scholar
  147. Robey RW, Massey PR, Amiri-Kordestani L, Bates SE (2010) ABC transporters: unvalidated therapeutic targets in cancer and the CNS. Anti Cancer Agents Med Chem 10:625–633CrossRefGoogle Scholar
  148. Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E et al (2012) Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 13:239–246CrossRefGoogle Scholar
  149. Rowinsky EK, Smith L, Wang YM, Chaturvedi P, Villalona M, Campbell E et al (1998) Phase I and pharmacokinetic study of paclitaxel in combination with biricodar, a novel agent that reverses multidrug resistance conferred by overexpression of both MDR1 and MRP. J Clin Oncol 16:2964–2976CrossRefGoogle Scholar
  150. Russel FG, Koenderink JB, Masereeuw R (2008) Multidrug resistance protein 4 (MRP4/ABCC4): a versatile efflux transporter for drugs and signalling molecules. Trends Pharmacol Sci 29:200–207CrossRefGoogle Scholar
  151. Sacha T (2014) Imatinib in chronic myeloid leukemia: an overview. Mediterr J Hematol Infect Dis 6:e2014007CrossRefPubMedPubMedCentralGoogle Scholar
  152. Schinkel AH, Smit JJ, van Tellingen O, Beijnen JH, Wagenaar E, van Deemter L et al (1994) Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 77:491–502CrossRefPubMedPubMedCentralGoogle Scholar
  153. Schinkel AH, Mayer U, Wagenaar E, Mol CA, van Deemter L, Smit JJ et al (1997) Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins. Proc Natl Acad Sci U S A 94:4028–4033CrossRefPubMedPubMedCentralGoogle Scholar
  154. Schlessinger J (2000) Cell signaling by receptor tyrosine kinases. Cell 103:211–225CrossRefGoogle Scholar
  155. Schmid KE, Davidson WS, Myatt L, Woollett LA (2003) Transport of cholesterol across a BeWo cell monolayer: implications for net transport of sterol from maternal to fetal circulation. J Lipid Res 44:1909–1918CrossRefGoogle Scholar
  156. Segaliny AI, Tellez-Gabriel M, Heymann MF, Heymann D (2015) Receptor tyrosine kinases: characterisation, mechanism of action and therapeutic interests for bone cancers. J Bone Oncol 4:1–12CrossRefPubMedPubMedCentralGoogle Scholar
  157. Serlin Y, Shelef I, Knyazer B, Friedman A (2015) Anatomy and physiology of the blood-brain barrier. Semin Cell Dev Biol 38:2–6CrossRefPubMedPubMedCentralGoogle Scholar
  158. Shen J, Carcaboso AM, Hubbard KE, Tagen M, Wynn HG, Panetta JC et al (2009a) Compartment-specific roles of ATP-binding cassette transporters define differential topotecan distribution in brain parenchyma and cerebrospinal fluid. Cancer Res 69:5885–5892CrossRefPubMedPubMedCentralGoogle Scholar
  159. Shen T, Kuang YH, Ashby CR, Lei Y, Chen A, Zhou Y et al (2009b) Imatinib and nilotinib reverse multidrug resistance in cancer cells by inhibiting the efflux activity of the MRP7 (ABCC10). PLoS One 4:e7520CrossRefPubMedPubMedCentralGoogle Scholar
  160. Shi Q, Zhang L, Liu M, Zhang X, Zhang X, Xu X et al (2015) Reversion of multidrug resistance by a pH-responsive cyclodextrin-derived nanomedicine in drug resistant cancer cells. Biomaterials 67:169–182CrossRefGoogle Scholar
  161. Shukla S, Sauna ZE, Ambudkar SV (2008a) Evidence for the interaction of imatinib at the transport-substrate site(s) of the multidrug-resistance-linked ABC drug transporters ABCB1 (P-glycoprotein) and ABCG2. Leukemia 22:445–447CrossRefGoogle Scholar
  162. Shukla S, Wu CP, Ambudkar SV (2008b) Development of inhibitors of ATP-binding cassette drug transporters: present status and challenges. Expert Opin Drug Metab Toxicol 4:205–223CrossRefGoogle Scholar
  163. Shukla S, Ohnuma S, Ambudkar SV (2011) Improving cancer chemotherapy with modulators of ABC drug transporters. Curr Drug Targets 12:621–630CrossRefPubMedPubMedCentralGoogle Scholar
  164. Shukla S, Chen ZS, Ambudkar SV (2012) Tyrosine kinase inhibitors as modulators of ABC transporter-mediated drug resistance. Drug Resist Updat 15:70–80CrossRefPubMedPubMedCentralGoogle Scholar
  165. Simoff I, Karlgren M, Backlund M, Lindstrom AC, Gaugaz FZ, Matsson P et al (2016) Complete knockout of endogenous Mdr1 (Abcb1) in MDCK cells by CRISPR-Cas9. J Pharm Sci 105:1017–1021CrossRefGoogle Scholar
  166. Slachtova L, Seda O, Behunova J, Mistrik M, Martasek P (2016) Genetic and biochemical study of dual hereditary jaundice: Dubin–Johnson and Gilbert’s syndromes. Haplotyping and founder effect of deletion in ABCC2. Eur J Hum Genet 24:704–709CrossRefGoogle Scholar
  167. Smith CH, Moe AJ, Ganapathy V (1992) Nutrient transport pathways across the epithelium of the placenta. Annu Rev Nutr 12:183–206CrossRefGoogle Scholar
  168. Smith G, Dawe RS, Clark C, Evans AT, Comrie MM, Wolf CR et al (2003) Quantitative real-time reverse transcription-polymerase chain reaction analysis of drug metabolizing and cytoprotective genes in psoriasis and regulation by ultraviolet radiation. J Invest Dermatol 121:390–398CrossRefGoogle Scholar
  169. Soldevilla MM, Villanueva H, Casares N, Lasarte JJ, Bendandi M, Inoges S et al (2016) MRP1-CD28 bi-specific oligonucleotide aptamers: target costimulation to drug-resistant melanoma cancer stem cells. Oncotarget 7:23182–23196CrossRefPubMedPubMedCentralGoogle Scholar
  170. Sosnik A (2013) 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 65:1828–1851CrossRefGoogle Scholar
  171. Sparreboom A, van Asperen J, Mayer U, Schinkel AH, Smit JW, Meijer DK et al (1997) Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc Natl Acad Sci U S A 94:2031–2035CrossRefPubMedPubMedCentralGoogle Scholar
  172. Stefkova J, Poledne R, Hubacek JA (2004) ATP-binding cassette (ABC) transporters in human metabolism and diseases. Physiol Res 53:235–243PubMedGoogle Scholar
  173. Stieger B, Gao B (2015) Drug transporters in the central nervous system. Clin Pharmacokinet 54:225–242CrossRefGoogle Scholar
  174. Stindt J(2011) Studies on ABC transporters from human liver in heterologous expression systems. https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=17058
  175. Sun YL, Patel A, Kumar P, Chen ZS (2012) Role of ABC transporters in cancer chemotherapy. Chin J Cancer 31:51–57CrossRefPubMedPubMedCentralGoogle Scholar
  176. Szakacs G, Varadi A, Ozvegy-Laczka C, Sarkadi B (2008) The role of ABC transporters in drug absorption, distribution, metabolism, excretion and toxicity (ADME-Tox). Drug Discov Today 13:379–393CrossRefGoogle Scholar
  177. Takechi T, Hirota T, Sakai T, Maeda N, Kobayashi D, Ieiri I (2018) Inter-individual differences in the expression of ABC and SLC family transporters in human skin: dna methylation regulates transcriptional activity of the human ABCC3 (MRP3) gene. Drug Metab Dispos 46:628–635CrossRefGoogle Scholar
  178. Takenaka S, Itoh T, Fujiwara R (2013) Expression pattern of human ATP-binding cassette transporters in skin. Pharmacol Res Perspect 1:e00005CrossRefPubMedPubMedCentralGoogle Scholar
  179. Tanaka H, Ohshima N, Ikenoya M, Komori K, Katoh F, Hidaka H (2003) HMN-176, an active metabolite of the synthetic antitumor agent HMN-214, restores chemosensitivity to multidrug-resistant cells by targeting the transcription factor NF-Y. Cancer Res 63:6942–6947PubMedGoogle Scholar
  180. Tao W, Zeng X, Liu T, Wang Z, Xiong Q, Ouyang C et al (2013) Docetaxel-loaded nanoparticles based on star-shaped mannitol-core PLGA-TPGS diblock copolymer for breast cancer therapy. Acta Biomater 9:8910–8920CrossRefGoogle Scholar
  181. Tetro N, Moushaev S, Rubinchik-Stern M, Eyal S (2018) The placental barrier: the gate and the fate in drug distribution. Pharm Res 35:71CrossRefGoogle Scholar
  182. Theodoulou FL, Kerr ID (2015) ABC transporter research: going strong 40 years on. Biochem Soc Trans 43:1033–1040CrossRefPubMedPubMedCentralGoogle Scholar
  183. Tidefelt U, Liliemark J, Gruber A, Liliemark E, Sundman-Engberg B, Juliusson G et al (2000) P-Glycoprotein inhibitor valspodar (PSC 833) increases the intracellular concentrations of daunorubicin in vivo in patients with P-glycoprotein-positive acute myeloid leukemia. J Clin Oncol 18:1837–1844CrossRefGoogle Scholar
  184. Tiwari AK, Sodani K, Wang SR, Kuang YH, Ashby CR, Chen X, Chen ZS (2009) Nilotinib (AMN107, Tasigna) reverses multidrug resistance by inhibiting the activity of the ABCB1/Pgp and ABCG2/BCRP/MXR transporters. Biochem Pharmacol 78:153–161CrossRefGoogle Scholar
  185. To KKW, Wu X, Yin C, Chai S, Yao S, Kadioglu O et al (2017) Reversal of multidrug resistance by Marsdenia tenacissima and its main active ingredients polyoxypregnanes. J Ethnopharmacol 203:110–119CrossRefGoogle Scholar
  186. Ueda K, Clark DP, Chen CJ, Roninson IB, Gottesman MM, Pastan I (1987) The human multidrug resistance (mdr1) gene. cDNA cloning and transcription initiation. J Biol Chem 262:505–508PubMedGoogle Scholar
  187. Uhlen M, Fagerberg L, Hallstrom BM, Lindskog C, Oksvold P, Mardinoglu A et al (2015) Proteomics. Tissue-based map of the human proteome. Science 347:1260419CrossRefPubMedPubMedCentralGoogle Scholar
  188. van Aubel RA, Smeets PH, Peters JG, Bindels RJ, Russel FG (2002) The MRP4/ABCC4 gene encodes a novel apical organic anion transporter in human kidney proximal tubules: putative efflux pump for urinary cAMP and cGMP. J Am Soc Nephrol 13:595–603PubMedGoogle Scholar
  189. van de Water FM, Masereeuw R, Russel FG (2005) Function and regulation of multidrug resistance proteins (MRPs) in the renal elimination of organic anions. Drug Metab Rev 37:443–471CrossRefGoogle Scholar
  190. van der Holt B, Lowenberg B, Burnett AK, Knauf WU, Shepherd J, Piccaluga PP et al (2005) The value of the MDR1 reversal agent PSC-833 in addition to daunorubicin and cytarabine in the treatment of elderly patients with previously untreated acute myeloid leukemia (AML), in relation to MDR1 status at diagnosis. Blood 106:2646–2654CrossRefGoogle Scholar
  191. van Vliet EA, van Schaik R, Edelbroek PM, Redeker S, Aronica E, Wadman WJ et al (2006) Inhibition of the multidrug transporter P-glycoprotein improves seizure control in phenytoin-treated chronic epileptic rats. Epilepsia 47:672–680CrossRefGoogle Scholar
  192. Vander Borght S, Komuta M, Libbrecht L, Katoonizadeh A, Aerts R, Dymarkowski S et al (2008) Expression of multidrug resistance-associated protein 1 in hepatocellular carcinoma is associated with a more aggressive tumour phenotype and may reflect a progenitor cell origin. Liver Int 28:1370–1380CrossRefGoogle Scholar
  193. Vasiliou V, Vasiliou K, Nebert DW (2009) Human ATP-binding cassette (ABC) transporter family. Hum Genomics 3:281–290CrossRefPubMedPubMedCentralGoogle Scholar
  194. Vlaming ML, Lagas JS, Schinkel AH (2009) Physiological and pharmacological roles of ABCG2 (BCRP): recent findings in Abcg2 knockout mice. Adv Drug Deliv Rev 61:14–25CrossRefGoogle Scholar
  195. Wandel C, Kim RB, Kajiji S, Guengerich P, Wilkinson GR, Wood AJ (1999) P-glycoprotein and cytochrome P-450 3A inhibition: dissociation of inhibitory potencies. Cancer Res 59:3944–3948PubMedGoogle Scholar
  196. Wang H, Gao Z (2018) Targeted production of reactive oxygen species in mitochondria to overcome cancer drug resistance. Nat Commun 9:562CrossRefPubMedPubMedCentralGoogle Scholar
  197. Wang S, Smith JD (2014) ABCA1 and nascent HDL biogenesis. Biofactors 40:547–554CrossRefPubMedPubMedCentralGoogle Scholar
  198. Wang H, Chen XP, Qiu FZ (2003) Overcoming multi-drug resistance by anti-MDR1 ribozyme. World J Gastroenterol 9:1444–1449PubMedGoogle Scholar
  199. Wang YJ, Zhang YK, Kathawala RJ, Chen ZS (2014) Repositioning of tyrosine kinase inhibitors as antagonists of ATP-binding cassette transporters in anticancer drug resistance. Cancers 6:1925–1952CrossRefPubMedPubMedCentralGoogle Scholar
  200. Warren KE, Patel MC, Mccully CM, Montuenga LM, Balis FM (2000) Effect of P-glycoprotein modulation with cyclosporin A on cerebrospinal fluid penetration of doxorubicin in non-human primates. Cancer Chemother Pharmacol 45:207–212CrossRefGoogle Scholar
  201. Weidner LD, Fung KL, Kannan P, Moen JK, Kumar JS, Mulder J et al (2016) Tariquidar is an inhibitor and not a substrate of human and mouse P-glycoprotein. Drug Metab Dispos 44:275–282CrossRefPubMedPubMedCentralGoogle Scholar
  202. Wells SA Jr, Santoro M (2009) Targeting the RET pathway in thyroid cancer. Clin Cancer Res 15:7119–7123CrossRefGoogle Scholar
  203. Wilkens S (2015) Structure and mechanism of ABC transporters. F1000Prime Rep 7:14CrossRefPubMedPubMedCentralGoogle Scholar
  204. Wlcek K, Stieger B (2014) ATP-binding cassette transporters in liver. Biofactors 40:188–198CrossRefGoogle Scholar
  205. Woodward OM, Kottgen A, Coresh J, Boerwinkle E, Guggino WB, Kottgen M (2009) Identification of a urate transporter, ABCG2, with a common functional polymorphism causing gout. Proc Natl Acad Sci U S A 106:10338–10342CrossRefPubMedPubMedCentralGoogle Scholar
  206. Woollett LA (2011) Review: transport of maternal cholesterol to the fetal circulation. Placenta 32:S218–S221CrossRefPubMedPubMedCentralGoogle Scholar
  207. Wu S, Fu L (2018) Tyrosine kinase inhibitors enhanced the efficacy of conventional chemotherapeutic agent in multidrug resistant cancer cells. Mol Cancer 17:25CrossRefPubMedPubMedCentralGoogle Scholar
  208. Wu CP, Calcagno AM, Ambudkar SV (2008) Reversal of ABC drug transporter-mediated multidrug resistance in cancer cells: evaluation of current strategies. Curr Mol Pharmacol 1:93–105CrossRefPubMedPubMedCentralGoogle Scholar
  209. Wu CP, Ohnuma S, Ambudkar SV (2011a) Discovering natural product modulators to overcome multidrug resistance in cancer chemotherapy. Curr Pharm Biotechnol 12:609–620CrossRefPubMedPubMedCentralGoogle Scholar
  210. Wu W, Dnyanmote AV, Nigam SK (2011b) Remote communication through solute carriers and ATP binding cassette drug transporter pathways: an update on the remote sensing and signaling hypothesis. Mol Pharmacol 79:795–805CrossRefPubMedPubMedCentralGoogle Scholar
  211. Xu ZP, Zeng QH, Lu GQ, Yu AB (2006) Inorganic nanoparticles as carriers for efficient cellular delivery. Chem Eng Sci 61:1027–1040CrossRefGoogle Scholar
  212. Yang M, Li W, Fan D, Yan Y, Zhang X, Zhang Y et al (2012) Expression of ABCB5 gene in hematological malignances and its significance. Leuk Lymphoma 53:1211–1215CrossRefGoogle Scholar
  213. Yang C, He X, Song L, Zhan X, Zhang Y, Dou J, Gu N (2014) Gamma-Fe2O3 nanoparticles increase therapeutic efficacy of combination with paclitaxel and anti-ABCG2 monoclonal antibody on multiple myeloma cancer stem cells in mouse model. J Biomed Nanotechnol 10:336–344CrossRefGoogle Scholar
  214. Zeng H, Bain LJ, Belinsky MG, Kruh GD (1999) Expression of multidrug resistance protein-3 (multispecific organic anion transporter-D) in human embryonic kidney 293 cells confers resistance to anticancer agents. Cancer Res 59:5964–5967PubMedGoogle Scholar
  215. Zhang X, Li F, Guo S, Chen X, Wang X, Li J et al (2014) Biofunctionalized polymer-lipid supported mesoporous silica nanoparticles for release of chemotherapeutics in multidrug resistant cancer cells. Biomaterials 35:3650–2665CrossRefGoogle Scholar
  216. Zhang G, Wang Z, Qian F, Zhao C, Sun C (2015) Silencing of the ABCC4 gene by RNA interference reverses multidrug resistance in human gastric cancer. Oncol Rep 33:1147–1154CrossRefGoogle Scholar
  217. Zhou G, Latchoumanin O, Hebbard L, Duan W, Liddle C, George J et al(2008) Aptamers as targeting ligands and therapeutic molecules for overcoming drug resistance in cancers. Adv Drug Deliv Rev. pii: S0169-409X(18)30057-7Google Scholar
  218. Zhu QL, Zhou Y, Guan M, Zhou XF, Yang SD, Liu Y et al (2014) Low-density lipoprotein-coupled N-succinyl chitosan nanoparticles co-delivering siRNA and doxorubicin for hepatocyte-targeted therapy. Biomaterials 35:5965–5976CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Haneen Amawi
    • 1
  • Hong-May Sim
    • 2
  • Amit K. Tiwari
    • 3
  • Suresh V. Ambudkar
    • 4
  • Suneet Shukla
    • 4
    Email author
  1. 1.Department of Pharmacy Practice, Faculty of PharmacyYarmouk UniversityIrbidJordan
  2. 2.Department of Pharmacy, Faculty of ScienceNational University of SingaporeSingaporeSingapore
  3. 3.Department of Pharmacology and Experimental Therapeutics, College of Pharmacy & Pharmaceutical SciencesUniversity of ToledoToledoUSA
  4. 4.Laboratory of Cell Biology, Center for Cancer ResearchNational Cancer Institute, National Institutes of HealthBethesdaUSA

Personalised recommendations