Targeting multidrug resistance in cancer
Tóm tắt
Từ khóa
Tài liệu tham khảo
Higgins, C. F. ABC transporters: from microorganisms to man. Annu. Rev. Cell Biol. 8, 67–113 (1992).
Ozvegy, C. et al. Functional characterization of the human multidrug transporter, ABCG2, expressed in insect cells. Biochem. Biophys. Res. Commun. 285, 111–117 (2001).
Chang, G. & Roth, C. B. Structure of MsbA from E. coli: a homolog of the multidrug resistance ATP binding cassette (ABC) transporters. Science 293, 1793–1800 (2001).
Dean, M., Rzhetsky, A. & Allikmets, R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res. 11, 1156–1166 (2001). Describes the phylogenetic relationship of the 48 human ABC transporters and the diseases caused by mutations in the genes encoding ABC transporters.
Lipinski, C. A., Lombardo, F., Dominy, B. W. & Feeney, P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 46, 3–26 (2001).
Schinkel, A. H. et al. 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, 491–502 (1994). Shows that mice lacking Mdr1a Pgp have altered pharmacokinetics for many drugs. This paper reports the first direct proof of the importance of ABC transporters for drug pharmacokinetics.
Schinkel, A. H. The physiological function of drug-transporting P-glycoproteins. Semin. Cancer Biol. 8, 161–170 (1997).
Kwan, P. & Brodie, M. J. Potential role of drug transporters in the pathogenesis of medically intractable epilepsy. Epilepsia 46, 224–235 (2005).
Yamazaki, M. et al. In vitro substrate identification studies for P-glycoprotein-mediated transport: species difference and predictability of in vivo results. J. Pharmacol. Exp. Ther. 296, 723–735 (2001).
Ambudkar, S. V. et al. Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu. Rev. Pharmacol. Toxicol. 39, 361–398 (1999).
Cordon-Cardo, C. et al. Expression of the multidrug resistance gene product (P-glycoprotein) in human normal and tumor tissues. J. Histochem. Cytochem. 38, 1277–1287 (1990).
Thiebaut, F. et al. Immunohistochemical localization in normal tissues of different epitopes in the multidrug transport protein P170: evidence for localization in brain capillaries and crossreactivity of one antibody with a muscle protein. J. Histochem. Cytochem. 37, 159–164 (1989).
Dano, K. Active outward transport of daunomycin in resistant Ehrlich ascites tumor cells. Biochim. Biophys. Acta 323, 466–483 (1973).
Tsuruo, T., Iida, H., Tsukagoshi, S. & Sakurai, Y. Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res. 41, 1967–1972 (1981). One of the first demonstrations that non-cytotoxic compounds could be used to reverse the activity of Pgp and formed the basis for the concept of 'engaging' the multidrug transporter to inactivate the protein.
Childs, S., Yeh, R. L., Georges, E. & Ling, V. Identification of a sister gene to P-glycoprotein. Cancer Res. 55, 2029–2034 (1995).
Gerloff, T. et al. The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver. J. Biol. Chem. 273, 10046–10050 (1998).
Ruetz, S. & Gros, P. Phosphatidylcholine translocase: a physiological role for the mdr2 gene. Cell 77, 1071–1081 (1994). Reports that some ABC transporters might be lipid flippases, which is consistent with a major hypothesis for the mechanism of action of Pgp as a drug flippase and extends the biological importance of ABC transporters.
van Helvoort, A. et al. MDR1 P-glycoprotein is a lipid translocase of broad specificity, while MDR3 P-glycoprotein specifically translocates phosphatidylcholine. Cell 87, 507–517 (1996).
Strautnieks, S. S. et al. A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nature Genet. 20, 233–238 (1998).
Childs, S., Yeh, R. L., Hui, D. & Ling, V. Taxol resistance mediated by transfection of the liver-specific sister gene of P-glycoprotein. Cancer Res. 58, 4160–4167 (1998).
Smith, A. J. et al. MDR3 P-glycoprotein, a phosphatidylcholine translocase, transports several cytotoxic drugs and directly interacts with drugs as judged by interference with nucleotide trapping. J. Biol. Chem. 275, 23530–23539 (2000).
Bakos, E. et al. Functional multidrug resistance protein (MRP1) lacking the N-terminal transmembrane domain. J. Biol. Chem. 273, 32167–32175 (1998).
Hipfner, D. R., Deeley, R. G. & Cole, S. P. Structural, mechanistic and clinical aspects of MRP1. Biochim. Biophys. Acta 1461, 359–376 (1999).
Szakacs, G. et al. Predicting drug sensitivity and resistance: profiling ABC transporter genes in cancer cells. Cancer Cell 6, 129–137 (2004). Applies a global approach to the analysis of the role of ABC transporters in drug resistance in cancer. The authors identified 28 transporters that could have a role in resistance to specific drugs, or classes of drugs. In addition, this paper introduces the concept of 'exploiting' multidrug transporters by identifying drugs that specifically kill Pgp-expressing cells.
Dietrich, C. G. et al. Mrp2-deficiency in the rat impairs biliary and intestinal excretion and influences metabolism and disposition of the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Carcinogenesis 22, 805–811 (2001).
Paulusma, C. C. et al. Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene. Science 271, 1126–1128 (1996).
Liedert, B., Materna, V., Schadendorf, D., Thomale, J. & Lage, H. Overexpression of cMOAT (MRP2/ABCC2) is associated with decreased formation of platinum-DNA adducts and decreased G2-arrest in melanoma cells resistant to cisplatin. J. Invest. Dermatol. 121, 172–176 (2003).
Koike, K. et al. A canalicular multispecific organic anion transporter (cMOAT) antisense cDNA enhances drug sensitivity in human hepatic cancer cells. Cancer Res. 57, 5475–5479 (1997).
Liu, J. et al. Overexpression of glutathione S-transferase II and multidrug resistance transport proteins is associated with acquired tolerance to inorganic arsenic. Mol. Pharmacol. 60, 302–309 (2001).
Annereau, J. P. et al. Analysis of ATP-binding cassette transporter expression in drug-selected cell lines by a microarray dedicated to multidrug resistance. Mol. Pharmacol. 66, 1397–1405 (2004).
Konig, J., Rost, D., Cui, Y. & Keppler, D. Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane. Hepatology 29, 1156–1163 (1999).
Scheffer, G. L. et al. Tissue distribution and induction of human multidrug resistant protein 3. Lab. Invest. 82, 193–201 (2002).
Zelcer, N. et al. Mice lacking Mrp3 (Abcc3) have normal bile salt transport, but altered hepatic transport of endogenous glucuronides. J. Hepatol. 9 Aug 2005 (10.1016/j.jhep.2005.07.022).
Belinsky, M. G. et al. Analysis of the in vivo functions of Mrp3. Mol. Pharmacol. 68, 160–168 (2005).
Kool, M. et al. Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines. Cancer Res. 57, 3537–3547 (1997).
Yamada, A., Kawano, K., Koga, M., Matsumoto, T. & Itoh, K. Multidrug resistance-associated protein 3 is a tumor rejection antigen recognized by HLA-A2402-restricted cytotoxic T lymphocytes. Cancer Res. 61, 6459–6466 (2001).
Young, L. C., Campling, B. G., Cole, S. P., Deeley, R. G. & Gerlach, J. H. Multidrug resistance proteins MRP3, MRP1, and MRP2 in lung cancer: correlation of protein levels with drug response and messenger RNA levels. Clin. Cancer Res. 7, 1798–1804 (2001).
Le Saux, O. et al. Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum. Nature Genet. 25, 223–227 (2000).
Belinsky, M. G., Chen, Z. S., Shchaveleva, I., Zeng, H. & Kruh, G. D. Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6). Cancer Res. 62, 6172–6177 (2002).
Hopper-Borge, E., Chen, Z. S., Shchaveleva, I., Belinsky, M. G. & Kruh, G. D. Analysis of the drug resistance profile of multidrug resistance protein 7 (ABCC10): resistance to docetaxel. Cancer Res. 64, 4927–4930 (2004).
Borst, P., Evers, R., Kool, M. & Wijnholds, J. A family of drug transporters: the multidrug resistance-associated proteins. J. Natl Cancer Inst. 92, 1295–1302 (2000).
Schuetz, J. D. et al. MRP4: a previously unidentified factor in resistance to nucleoside-based antiviral drugs. Nature Med. 5, 1048–1051 (1999).
Guo, Y. et al. MRP8, ATP-binding cassette C11 (ABCC11), is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines 2′,3′-dideoxycytidine and 9′-(2′-phosphonylmethoxyethyl)adenine. J. Biol. Chem. 278, 29509–29514 (2003).
Chen, Z. S., Guo, Y., Belinsky, M. G., Kotova, E. & Kruh, G. D. Transport of bile acids, sulfated steroids, estradiol 17-β-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11). Mol. Pharmacol. 67, 545–557 (2005).
Abbott, B. L. ABCG2 (BCRP) expression in normal and malignant hematopoietic cells. Hematol. Oncol. 21, 115–130 (2003).
Schinkel, A. H. & Jonker, J. W. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv. Drug Deliv. Rev. 55, 3–29 (2003).
Kawabata, S. et al. Breast cancer resistance protein directly confers SN-38 resistance of lung cancer cells. Biochem. Biophys. Res. Commun. 280, 1216–1223 (2001).
Ozvegy-Laczka, C., Cserepes, J., Elkind, N. B. & Sarkadi, B. Tyrosine kinase inhibitor resistance in cancer: role of ABC multidrug transporters. Drug Resist. Updat. 8, 15–26 (2005).
Gottesman, M. M., Fojo, T. & Bates, S. E. Multidrug resistance in cancer: role of ATP-dependent transporters. Nature Rev. Cancer 2, 48–58 (2002). A concise review on ABC transporters that confer MDR to cancer cells.
Leonard, G. D., Fojo, T. & Bates, S. E. The role of ABC transporters in clinical practice. Oncologist 8, 411–424 (2003).
Trock, B. J., Leonessa, F. & Clarke, R. Multidrug resistance in breast cancer: a meta-analysis of MDR1/gp170 expression and its possible functional significance. J. Natl Cancer Inst. 89, 917–931 (1997).
Abolhoda, A. et al. Rapid activation of MDR1 gene expression in human metastatic sarcoma after in vivo exposure to doxorubicin. Clin. Cancer Res. 5, 3352–3356 (1999).
Szakacs, G., Jakab, K., Antal, F. & Sarkadi, B. Diagnostics of multidrug resistance in cancer. Pathol. Oncol. Res. 4, 251–257 (1998).
Pallis, M. & Das-Gupta, E. Flow cytometric measurement of functional and phenotypic P-glycoprotein. Methods Mol. Med. 111, 167–181 (2005).
Karaszi, E. et al. Calcein assay for multidrug resistance reliably predicts therapy response and survival rate in acute myeloid leukaemia. Br. J. Haematol. 112, 308–314 (2001).
Pallis, M. & Russell, N. Strategies for overcoming p-glycoprotein-mediated drug resistance in acute myeloblastic leukaemia. Leukemia 18, 1927–1930 (2004).
van der Holt, B. et al. 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, 2646–2654 (2005).
Leith, C. P. et al. Frequency and clinical significance of the expression of the multidrug resistance proteins MDR1/P-glycoprotein, MRP1, and LRP in acute myeloid leukemia: a Southwest Oncology Group Study. Blood 94, 1086–1099 (1999).
Berger, W. et al. Multidrug resistance markers P-glycoprotein, multidrug resistance protein 1, and lung resistance protein in non-small cell lung cancer: prognostic implications. J. Cancer Res. Clin. Oncol. 131, 355–363 (2005).
Michieli, M. et al. P-glycoprotein (PGP), lung resistance-related protein (LRP) and multidrug resistance-associated protein (MRP) expression in acute promyelocytic leukaemia. Br. J. Haematol. 108, 703–709 (2000).
Filipits, M. et al. Clinical role of multidrug resistance protein 1 expression in chemotherapy resistance in early-stage breast cancer: the Austrian Breast and Colorectal Cancer Study Group. J. Clin. Oncol. 23, 1161–1168 (2005).
Ross, D. D. Modulation of drug resistance transporters as a strategy for treating myelodysplastic syndrome. Best Pract. Res. Clin. Haematol. 17, 641–651 (2004).
Dean, M., Fojo, T. & Bates, S. Tumour stem cells and drug resistance. Nature Rev. Cancer 5, 275–284 (2005).
Raaijmakers, M. H. et al. Breast cancer resistance protein in drug resistance of primitive CD34+38– cells in acute myeloid leukemia. Clin. Cancer Res. 11, 2436–2444 (2005).
List, A. F. et al. Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group study. Blood 98, 3212–3220 (2001). The first study to show that addition of cyclosporine to AML (known to be Pgp positive) therapy improves response in poor-risk patients.
Wattel, E. et al. Quinine improves results of intensive chemotherapy (IC) in myelodysplastic syndromes (MDS) expressing P-glycoprotein (PGP). Updated results of a randomized study. Groupe Français des Myélodysplasies (GFM) and Groupe GOELAMS. Adv. Exp. Med. Biol. 457, 35–46 (1999).
Daenen, S. et al. Addition of cyclosporin A to the combination of mitoxantrone and etoposide to overcome resistance to chemotherapy in refractory or relapsing acute myeloid leukaemia; a randomised phase II trial from HOVON, the Dutch-Belgian Haemato-Oncology Working Group for adults. Leuk. Res. 28, 1057–1067 (2004).
Hollt, V., Kouba, M., Dietel, M. & Vogt, G. Stereoisomers of calcium antagonists which differ markedly in their potencies as calcium blockers are equally effective in modulating drug transport by P-glycoprotein. Biochem. Pharmacol. 43, 2601–2608 (1992).
Baer, M. R. et al. Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720. Blood 100, 1224–1232 (2002).
Kolitz, J. E. et al. Dose escalation studies of cytarabine, daunorubicin, and etoposide with and without multidrug resistance modulation with PSC-833 in untreated adults with acute myeloid leukemia younger than 60 years: final induction results of Cancer and Leukemia Group B Study 9621. J. Clin. Oncol. 22, 4290–4301 (2004).
Goldman, B. Multidrug resistance: can new drugs help chemotherapy score against cancer? J. Natl Cancer Inst. 95, 255–257 (2003).
Product Development Pipeline — November 2004 [online], <http://www.glaxosmithkline.de/content/forschung/pipeline-dec2004.pdf> (2004).
Guns, E. S., Denyssevych, T., Dixon, R., Bally, M. B. & Mayer, L. Drug interaction studies between paclitaxel (Taxol) and OC144-093 — a new modulator of MDR in cancer chemotherapy. Eur. J. Drug Metab. Pharmacokinet. 27, 119–126 (2002).
Stewart, A. et al. Phase I trial of XR9576 in healthy volunteers demonstrates modulation of P-glycoprotein in CD56+ lymphocytes after oral and intravenous administration. Clin. Cancer Res. 6, 4186–4191 (2000). Uses a surrogate marker for inhibition of Pgp (Pgp-positive CD56 lymphocytes) to show activity of a third-generation Pgp inhibitor (XR9576) in vivo.
Minderman, H., O'Loughlin, K. L., Pendyala, L. & Baer, M. R. VX-710 (biricodar) increases drug retention and enhances chemosensitivity in resistant cells overexpressing P-glycoprotein, multidrug resistance protein, and breast cancer resistance protein. Clin. Cancer Res. 10, 1826–1834 (2004).
Xenova Group Limited Tariquidar [online], < http://www.xenova.co.uk/dc_xr9576.html > (2006).
van Zuylen, L., Nooter, K., Sparreboom, A. & Verweij, J. Development of multidrug-resistance convertors: sense or nonsense? Invest. New Drugs 18, 205–220 (2000).
Dantzig, A. H., de Alwis, D. P. & Burgess, M. Considerations in the design and development of transport inhibitors as adjuncts to drug therapy. Adv. Drug Deliv. Rev. 55, 133–150 (2003).
Loo, T. W. & Clarke, D. M. Blockage of drug resistance in vitro by disulfiram, a drug used to treat alcoholism. J. Natl Cancer Inst. 92, 898–902 (2000).
Zhou, S., Lim, L. Y. & Chowbay, B. Herbal modulation of P-glycoprotein. Drug Metab. Rev. 36, 57–104 (2004).
Seelig, A. & Gatlik-Landwojtowicz, E. Inhibitors of multidrug efflux transporters: their membrane and protein interactions. Mini Rev. Med. Chem. 5, 135–151 (2005).
Pleban, K. & Ecker, G. F. Inhibitors of p-glycoprotein — lead identification and optimisation. Mini Rev. Med. Chem. 5, 153–163 (2005).
Sharom, F. J. et al. Interaction of the P-glycoprotein multidrug transporter (MDR1) with high affinity peptide chemosensitizers in isolated membranes, reconstituted systems, and intact cells. Biochem. Pharmacol. 58, 571–586 (1999).
Tarasova, N. I., Rice, W. G. & Michejda, C. J. Inhibition of G-protein-coupled receptor function by disruption of transmembrane domain interactions. J. Biol. Chem. 274, 34911–34915 (1999).
George, S. R. et al. Blockade of G protein-coupled receptors and the dopamine transporter by a transmembrane domain peptide: novel strategy for functional inhibition of membrane proteins in vivo. J. Pharmacol. Exp. Ther. 307, 481–489 (2003).
Tarasova, N. I. et al. Transmembrane inhibitors of P-glycoprotein, an ABC transporter. J. Med. Chem. 48, 3768–3775 (2005).
Mechetner, E. B. & Roninson, I. B. Efficient inhibition of P-glycoprotein-mediated multidrug resistance with a monoclonal antibody. Proc. Natl Acad. Sci. USA 89, 5824–5828 (1992).
Pawlak-Roblin, C. et al. Inhibition of multidrug resistance by immunisation with synthetic P-glycoprotein-derived peptides. Eur. J. Cancer 40, 606–613 (2004).
Kang, H. et al. Inhibition of MDR1 gene expression by chimeric HNA antisense oligonucleotides. Nucleic Acids Res. 32, 4411–4419 (2004).
Bartsevich, V. V. & Juliano, R. L. Regulation of the MDR1 gene by transcriptional repressors selected using peptide combinatorial libraries. Mol. Pharmacol. 58, 1–10 (2000).
Xu, D., Ye, D., Fisher, M. & Juliano, R. L. Selective inhibition of P-glycoprotein expression in multidrug-resistant tumor cells by a designed transcriptional regulator. J. Pharmacol. Exp. Ther. 302, 963–971 (2002).
Synold, T. W., Dussault, I. & Forman, B. M. The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nature Med. 7, 584–590 (2001).
Xu, D., Kang, H., Fisher, M. & Juliano, R. L. Strategies for inhibition of MDR1 gene expression. Mol. Pharmacol. 66, 268–275 (2004).
Pichler, A., Zelcer, N., Prior, J. L., Kuil, A. J. & Piwnica-Worms, D. In vivo RNA interference-mediated ablation of MDR1 P-glycoprotein. Clin. Cancer Res. 11, 4487–4494 (2005).
Perego, P. et al. A novel 7-modified camptothecin analog overcomes breast cancer resistance protein-associated resistance in a mitoxantrone-selected colon carcinoma cell line. Cancer Res. 61, 6034–6037 (2001).
Lampidis, T. J. et al. Circumvention of P-GP MDR as a function of anthracycline lipophilicity and charge. Biochemistry 36, 2679–2685 (1997).
Byrne, J. L. et al. Early allogeneic transplantation for refractory or relapsed acute leukaemia following remission induction with FLAG. Leukemia 13, 786–791 (1999).
Vail, D. M. et al. Pegylated liposomal doxorubicin: proof of principle using preclinical animal models and pharmacokinetic studies. Semin. Oncol. 31, 16–35 (2004).
Krishna, R., St-Louis, M. & Mayer, L. D. Increased intracellular drug accumulation and complete chemosensitization achieved in multidrug-resistant solid tumors by co-administering valspodar (PSC 833) with sterically stabilized liposomal doxorubicin. Int. J. Cancer 85, 131–141 (2000).
Fracasso, P. M. et al. Phase I study of pegylated liposomal doxorubicin and the multidrug-resistance modulator, valspodar. Br. J. Cancer 93, 46–53 (2005).
Gao, Z., Fain, H. D. & Rapoport, N. Ultrasound-enhanced tumor targeting of polymeric micellar drug carriers. Mol. Pharm. 1, 317–330 (2004).
Mahadevan, D. & List, A. F. Targeting the multidrug resistance-1 transporter in AML: molecular regulation and therapeutic strategies. Blood 104, 1940–1951 (2004).
Licht, T., Goldenberg, S. K., Vieira, W. D., Gottesman, M. M. & Pastan, I. Drug selection of MDR1-transduced hematopoietic cells ex vivo increases transgene expression and chemoresistance in reconstituted bone marrow in mice. Gene Ther. 7, 348–358 (2000).
Blagosklonny, M. V. How cancer could be cured by 2015. Cell Cycle 4, 269–278 (2005).
Blagosklonny, M. V. Treatment with inhibitors of caspases, that are substrates of drug transporters, selectively permits chemotherapy-induced apoptosis in multidrug-resistant cells but protects normal cells. Leukemia 15, 936–941 (2001).
FitzGerald, D. J. et al. A monoclonal antibody–Pseudomonas toxin conjugate that specifically kills multidrug-resistant cells. Proc. Natl Acad. Sci. USA 84, 4288–4292 (1987).
Heike, Y. et al. Monoclonal anti-P-glycoprotein antibody-dependent killing of multidrug-resistant tumor cells by human mononuclear cells. Jpn. J. Cancer Res. 81, 1155–1161 (1990).
Morizono, K. et al. Lentiviral vector retargeting to P-glycoprotein on metastatic melanoma through intravenous injection. Nature Med. 11, 346–352 (2005).
Warr, J. R., Quinn, D., Elend, M. & Fenton, J. A. Gain and loss of hypersensitivity to resistance modifiers in multidrug resistant Chinese hamster ovary cells. Cancer Lett. 98, 115–120 (1995).
Lehne, G., De Angelis, P., den Boer, M. & Rugstad, H. E. Growth inhibition, cytokinesis failure and apoptosis of multidrug-resistant leukemia cells after treatment with P-glycoprotein inhibitory agents. Leukemia 13, 768–778 (1999).
Lehne, G. et al. The cyclosporin PSC 833 increases survival and delays engraftment of human multidrug-resistant leukemia cells in xenotransplanted NOD-SCID mice. Leukemia 16, 2388–2394 (2002).
Kaplan, O. et al. The multidrug resistance phenotype: 31P nuclear magnetic resonance characterization and 2-deoxyglucose toxicity. Cancer Res. 51, 1638–1644 (1991).
Bell, S. E., Quinn, D. M., Kellett, G. L. & Warr, J. R. 2-Deoxy-D-glucose preferentially kills multidrug-resistant human KB carcinoma cell lines by apoptosis. Br. J. Cancer 78, 1464–1470 (1998).
Bentley, J., Quinn, D. M., Pitman, R. S., Warr, J. R. & Kellett, G. L. The human KB multidrug-resistant cell line KB-C1 is hypersensitive to inhibitors of glycosylation. Cancer Lett. 115, 221–227 (1997).
Warr, J. R., Bamford, A. & Quinn, D. M. The preferential induction of apoptosis in multidrug-resistant KB cells by 5-fluorouracil. Cancer Lett. 175, 39–44 (2002).
Monks, A. et al. Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J. Natl Cancer Inst. 83, 757–766 (1991).
Johnstone, R. W., Ruefli, A. A. & Smyth, M. J. Multiple physiological functions for multidrug transporter P-glycoprotein? Trends Biochem. Sci. 25, 1–6 (2000).
Turzanski, J., Grundy, M., Shang, S., Russell, N. & Pallis, M. P-glycoprotein is implicated in the inhibition of ceramide-induced apoptosis in TF-1 acute myeloid leukemia cells by modulation of the glucosylceramide synthase pathway. Exp. Hematol. 33, 62–72 (2005).
Lucci, A., Han, T. Y., Liu, Y. Y., Giuliano, A. E. & Cabot, M. C. Multidrug resistance modulators and doxorubicin synergize to elevate ceramide levels and elicit apoptosis in drug-resistant cancer cells. Cancer 86, 300–311 (1999).
Trompier, D. et al. Verapamil and its derivative trigger apoptosis through glutathione extrusion by multidrug resistance protein MRP1. Cancer Res. 64, 4950–4956 (2004).
Meerum Terwogt, J. M. et al. Coadministration of oral cyclosporin A enables oral therapy with paclitaxel. Clin. Cancer Res. 5, 3379–3384 (1999).
Lepper, E. R. et al. Mechanisms of resistance to anticancer drugs: the role of the polymorphic ABC transporters ABCB1 and ABCG2. Pharmacogenomics 6, 115–138 (2005).
Juliano, R. L. & Ling, V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim. Biophys. Acta 455, 152–162 (1976).
Chen, C. J. et al. Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell 47, 381–389 (1986). Includes the sequence of the first cloned human ABC transporter, MDR1 (Pgp) and shows its homology to two known nutrient transporters in bacteria, MalK (maltose transporter ATP-binding subunit) and HisP (histidine transporter ATP-binding subunit).
Ueda, K., Cardarelli, C., Gottesman, M. M. & Pastan, I. Expression of a full-length cDNA for the human 'MDR1' gene confers resistance to colchicine, doxorubicin, and vinblastine. Proc. Natl Acad. Sci. USA 84, 3004–3008 (1987).
Gerlach, J. H. et al. Homology between P-glycoprotein and a bacterial haemolysin transport protein suggests a model for multidrug resistance. Nature 324, 485–489 (1986).
Shen, D. W. et al. Multiple drug-resistant human KB carcinoma cells independently selected for high-level resistance to colchicine, adriamycin, or vinblastine show changes in expression of specific proteins. J. Biol. Chem. 261, 7762–7770 (1986).
Gros, P., Croop, J. & Housman, D. Mammalian multidrug resistance gene: complete cDNA sequence indicates strong homology to bacterial transport proteins. Cell 47, 371–380 (1986).
McGrath, T. & Center, M. S. Mechanisms of multidrug resistance in HL60 cells: evidence that a surface membrane protein distinct from P-glycoprotein contributes to reduced cellular accumulation of drug. Cancer Res. 48, 3959–3963 (1988).
Mirski, S. E., Gerlach, J. H. & Cole, S. P. Multidrug resistance in a human small cell lung cancer cell line selected in adriamycin. Cancer Res. 47, 2594–2598 (1987).
Cole, S. P. Patterns of cross-resistance in a multidrug-resistant small-cell lung carcinoma cell line. Cancer Chemother. Pharmacol. 26, 250–256 (1990).
Cole, S. P. et al. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science 258, 1650–1654 (1992). Describes the characterization of the second member of the ABC transporter family that can confer MDR (MRP1 or ABCC1), changing the paradigm of MDR.
Doyle, L. A. et al. A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc. Natl Acad. Sci. USA 95, 15665–15670 (1998).
Allikmets, R., Schriml, L. M., Hutchinson, A., Romano-Spica, V. & Dean, M. A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance. Cancer Res. 58, 5337–5339 (1998).
Miyake, K. et al. Molecular cloning of cDNAs which are highly overexpressed in mitoxantrone-resistant cells: demonstration of homology to ABC transport genes. Cancer Res. 59, 8–13 (1999).
Sarkadi, B., Price, E. M., Boucher, R. C., Germann, U. A. & Scarborough, G. A. Expression of the human multidrug resistance cDNA in insect cells generates a high activity drug-stimulated membrane ATPase. J. Biol. Chem. 267, 4854–4858 (1992).
Garrigues, A., Nugier, J., Orlowski, S. & Ezan, E. A high-throughput screening microplate test for the interaction of drugs with P-glycoprotein. Anal. Biochem. 305, 106–114 (2002).
Lin, J. H. & Yamazaki, M. Clinical relevance of P-glycoprotein in drug therapy. Drug Metab. Rev. 35, 417–454 (2003).
Relling, M. V. Are the major effects of P-glycoprotein modulators due to altered pharmacokinetics of anticancer drugs? Ther. Drug Monit. 18, 350–356 (1996).
Benet, L. Z., Cummins, C. L. & Wu, C. Y. Unmasking the dynamic interplay between efflux transporters and metabolic enzymes. Int. J. Pharm. 277, 3–9 (2004).
Bohme, M., Buchler, M., Muller, M. & Keppler, D. Differential inhibition by cyclosporins of primary-active ATP-dependent transporters in the hepatocyte canalicular membrane. FEBS Lett. 333, 193–196 (1993).
Liscovitch, M. & Lavie, Y. Cancer multidrug resistance: a review of recent drug discovery research. IDrugs 5, 349–355 (2002).
Hegewisch-Becker, S. MDR1 reversal: criteria for clinical trials designed to overcome the multidrug resistance phenotype. Leukemia 10 (Suppl. 3), 32–38 (1996).
Beck, W. T. & Grogan, T. M. Methods to detect P-glycoprotein and implications for other drug resistance-associated proteins. Leukemia 11, 1107–1109 (1997).
Marie, J. P. et al. Measuring multidrug resistance expression in human malignancies: elaboration of consensus recommendations. Semin. Hematol. 34, 63–71 (1997).
Agrawal, M. et al. Increased 99mTc-sestamibi accumulation in normal liver and drug-resistant tumors after the administration of the glycoprotein inhibitor, XR9576. Clin. Cancer Res. 9, 650–656 (2003).
Leslie, E. M., Deeley, R. G. & Cole, S. P. Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicol. Appl. Pharmacol. 204, 216–237 (2005).
Maliepaard, M. et al. Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res. 61, 3458–3464 (2001).
Mottino, A. D., Hoffman, T., Jennes, L. & Vore, M. Expression and localization of multidrug resistant protein mrp2 in rat small intestine. J. Pharmacol. Exp. Ther. 293, 717–723 (2000).
Thiebaut, F. et al. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc. Natl Acad. Sci. USA 84, 7735–7738 (1987).
Scheffer, G. L. et al. Multidrug resistance related molecules in human and murine lung. J. Clin. Pathol. 55, 332–339 (2002).
Peng, K. C. et al. Tissue and cell distribution of the multidrug resistance-associated protein (MRP) in mouse intestine and kidney. J. Histochem. Cytochem. 47, 757–768 (1999).
Chandra, P. & Brouwer, K. L. The complexities of hepatic drug transport: current knowledge and emerging concepts. Pharm. Res. 21, 719–735 (2004).
Ros, J. E., Libbrecht, L., Geuken, M., Jansen, P. L. & Roskams, T. A. High expression of MDR1, MRP1, and MRP3 in the hepatic progenitor cell compartment and hepatocytes in severe human liver disease. J. Pathol. 200, 553–560 (2003).
Ros, J. E. et al. ATP binding cassette transporter gene expression in rat liver progenitor cells. Gut 52, 1060–1067 (2003).
Mizuno, N. et al. Impaired renal excretion of 6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl) benzothiazole (E3040) sulfate in breast cancer resistance protein (BCRP1/ABCG2) knockout mice. Drug Metab. Dispos. 32, 898–901 (2004).
Atkinson, D. E., Greenwood, S. L., Sibley, C. P., Glazier, J. D. & Fairbairn, L. J. Role of MDR1 and MRP1 in trophoblast cells, elucidated using retroviral gene transfer. Am. J. Physiol. Cell Physiol. 285, C584–C591 (2003).
Ronaldson, P. T., Bendayan, M., Gingras, D., Piquette-Miller, M. & Bendayan, R. Cellular localization and functional expression of P-glycoprotein in rat astrocyte cultures. J. Neurochem. 89, 788–800 (2004).
Rao, V. V. et al. Choroid plexus epithelial expression of MDR1 P glycoprotein and multidrug resistance-associated protein contribute to the blood–cerebrospinal-fluid drug-permeability barrier. Proc. Natl Acad. Sci. USA 96, 3900–3905 (1999).
Sugiyama, D., Kusuhara, H., Lee, Y. J. & Sugiyama, Y. Involvement of multidrug resistance associated protein 1 (Mrp1) in the efflux transport of 17β estradiol-D-17β-glucuronide (E217βG) across the blood–brain barrier. Pharm. Res. 20, 1394–1400 (2003).
Zhang, Y., Schuetz, J. D., Elmquist, W. F. & Miller, D. W. Plasma membrane localization of multidrug resistance-associated protein homologs in brain capillary endothelial cells. J. Pharmacol. Exp. Ther. 311, 449–455 (2004).
Leggas, M. et al. Mrp4 confers resistance to topotecan and protects the brain from chemotherapy. Mol. Cell Biol. 24, 7612–7621 (2004).
Dombrowski, S. M. et al. Overexpression of multiple drug resistance genes in endothelial cells from patients with refractory epilepsy. Epilepsia 42, 1501–1506 (2001).
Potschka, H., Fedrowitz, M. & Loscher, W. Brain access and anticonvulsant efficacy of carbamazepine, lamotrigine, and felbamate in ABCC2/MRP2-deficient TR-rats. Epilepsia 44, 1479–1486 (2003).
Potschka, H., Fedrowitz, M. & Loscher, W. Multidrug resistance protein MRP2 contributes to blood–brain barrier function and restricts antiepileptic drug activity. J. Pharmacol. Exp. Ther. 306, 124–131 (2003).
Jonker, J. W. et al. Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. J. Natl Cancer Inst. 92, 1651–1656 (2000).
St-Pierre, M. V. et al. Expression of members of the multidrug resistance protein family in human term placenta. Am. J. Physiol. Regul. Integr. Comp. Physiol. 279, R1495–R1503 (2000).
Madon, J., Hagenbuch, B., Landmann, L., Meier, P. J. & Stieger, B. Transport function and hepatocellular localization of mrp6 in rat liver. Mol. Pharmacol. 57, 634–641 (2000).
Jonker, J. W. et al. The breast cancer resistance protein BCRP (ABCG2) concentrates drugs and carcinogenic xenotoxins into milk. Nature Med. 11, 127–129 (2005). Analysis of Abcg2 -knockout mice that reveals a surprising role of ABCG2 (BCRP) in concentrating drugs and carcinogenic xenotoxins into breast milk.
Haimeur, A., Conseil, G., Deeley, R. G. & Cole, S. P. The MRP-related and BCRP/ABCG2 multidrug resistance proteins: biology, substrate specificity and regulation. Curr. Drug Metab. 5, 21–53 (2004).
Tribull, T. E., Bruner, R. H. & Bain, L. J. The multidrug resistance-associated protein 1 transports methoxychlor and protects the seminiferous epithelium from injury. Toxicol. Lett. 142, 61–70 (2003).
Melaine, N. et al. Multidrug resistance genes and p-glycoprotein in the testis of the rat, mouse, Guinea pig, and human. Biol. Reprod. 67, 1699–1707 (2002).
Zhou, S. et al. The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nature Med. 7, 1028–1034 (2001).
Van Aubel, R. A., Smeets, P. H., van den Heuvel, J. J. & Russel, F. G. Human organic anion transporter MRP4 (ABCC4) is an efflux pump for the purine end metabolite urate with multiple allosteric substrate binding sites. Am. J. Physiol. Renal Physiol. 288, F327–F333 (2005).
Rius, M., Nies, A. T., Hummel-Eisenbeiss, J., Jedlitschky, G. & Keppler, D. Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane. Hepatology 38, 374–384 (2003).
Laing, N. M. et al. Amplification of the ATP-binding cassette 2 transporter gene is functionally linked with enhanced efflux of estramustine in ovarian carcinoma cells. Cancer Res. 58, 1332–1337 (1998).
Vulevic, B. et al. Cloning and characterization of human adenosine 5′-triphosphate-binding cassette, sub-family A, transporter 2 (ABCA2). Cancer Res. 61, 3339–3347 (2001).
Boonstra, R. et al. Mitoxantrone resistance in a small cell lung cancer cell line is associated with ABCA2 upregulation. Br. J. Cancer 90, 2411–2417 (2004).
Tanigawara, Y. et al. Transport of digoxin by human P-glycoprotein expressed in a porcine kidney epithelial cell line (LLC-PK1). J. Pharmacol. Exp. Ther. 263, 840–845 (1992).
Kim, R. B. et al. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J. Clin. Invest. 101, 289–294 (1998).
Norris, M. D. et al. Involvement of MDR1 P-glycoprotein in multifactorial resistance to methotrexate. Int. J. Cancer 65, 613–619 (1996).
Lee, C. G. et al. HIV-1 protease inhibitors are substrates for the MDR1 multidrug transporter. Biochemistry 37, 3594–3601 (1998).
Hegedus, T. et al. Interaction of tyrosine kinase inhibitors with the human multidrug transporter proteins, MDR1 and MRP1. Biochim. Biophys. Acta 1587, 318–325 (2002).
Zhang, X. P. et al. P-glycoprotein mediates profound resistance to bisantrene. Oncol. Res. 6, 291–301 (1994).
Hooijberg, J. H. et al. Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2. Cancer Res. 59, 2532–2535 (1999).
Cui, Y. et al. Drug resistance and ATP-dependent conjugate transport mediated by the apical multidrug resistance protein, MRP2, permanently expressed in human and canine cells. Mol. Pharmacol. 55, 929–937 (1999).
Bakos, E. et al. Interactions of the human multidrug resistance proteins MRP1 and MRP2 with organic anions. Mol. Pharmacol. 57, 760–768 (2000).
Zeng, H., Chen, Z. S., Belinsky, M. G., Rea, P. A. & Kruh, G. D. Transport of methotrexate (MTX) and folates by multidrug resistance protein (MRP) 3 and MRP1: effect of polyglutamylation on MTX transport. Cancer Res. 61, 7225–7232 (2001).
Renes, J., de Vries, E. G., Nienhuis, E. F., Jansen, P. L. & Muller, M. ATP- and glutathione-dependent transport of chemotherapeutic drugs by the multidrug resistance protein MRP1. Br. J. Pharmacol. 126, 681–688 (1999).
Klappe, K., Hinrichs, J. W., Kroesen, B. J., Sietsma, H. & Kok, J. W. MRP1 and glucosylceramide are coordinately over expressed and enriched in rafts during multidrug resistance acquisition in colon cancer cells. Int. J. Cancer 110, 511–522 (2004).
Zaman, G. J. et al. Role of glutathione in the export of compounds from cells by the multidrug-resistance-associated protein. Proc. Natl Acad. Sci. USA 92, 7690–7694 (1995).
Luo, F. R., Paranjpe, P. V., Guo, A., Rubin, E. & Sinko, P. Intestinal transport of irinotecan in Caco-2 cells and MDCK II cells overexpressing efflux transporters Pgp, cMOAT, and MRP1. Drug Metab. Dispos. 30, 763–770 (2002).
Chu, X. Y. et al. Multispecific organic anion transporter is responsible for the biliary excretion of the camptothecin derivative irinotecan and its metabolites in rats. J. Pharmacol. Exp. Ther. 281, 304–314 (1997).
Chu, X. Y. et al. Biliary excretion mechanism of CPT-11 and its metabolites in humans: involvement of primary active transporters. Cancer Res. 58, 5137–5143 (1998).
Norris, M. D. et al. Expression of multidrug transporter MRP4/ABCC4 is a marker of poor prognosis in neuroblastoma and confers resistance to irinotecan in vitro. Mol. Cancer Ther. 4, 547–553 (2005).
Yang, C. J., Horton, J. K., Cowan, K. H. & Schneider, E. Cross-resistance to camptothecin analogues in a mitoxantrone-resistant human breast carcinoma cell line is not due to DNA topoisomerase I alterations. Cancer Res. 55, 4004–4009 (1995).
Tian, Q. et al. Human multidrug resistance associated protein 4 confers resistance to camptothecins. Pharm. Res. 22, 1837–1853 (2005).
Yang, C. H. et al. BCRP/MXR/ABCP expression in topotecan-resistant human breast carcinoma cells. Biochem. Pharmacol. 60, 831–837 (2000).
Chu, X. Y. et al. Active efflux of CPT-11 and its metabolites in human KB-derived cell lines. J. Pharmacol. Exp. Ther. 288, 735–741 (1999).
Chen, Z. S., Lee, K. & Kruh, G. D. Transport of cyclic nucleotides and estradiol 17-β-D-glucuronide by multidrug resistance protein 4. Resistance to 6-mercaptopurine and 6-thioguanine. J. Biol. Chem. 276, 33747–33754 (2001).
Huisman, M. T., Chhatta, A. A., van Tellingen, O., Beijnen, J. H. & Schinkel, A. H. MRP2 (ABCC2) transports taxanes and confers paclitaxel resistance and both processes are stimulated by probenecid. Int. J. Cancer 116, 824–829 (2005).
Dietrich, C. G., Ottenhoff, R., de Waart, D. R. & Oude Elferink, R. P. Role of MRP2 and GSH in intrahepatic cycling of toxins. Toxicology 167, 73–81 (2001).
Jorajuria, S. et al. ATP binding cassette multidrug transporters limit the anti-HIV activity of zidovudine and indinavir in infected human macrophages. Antivir. Ther. 9, 519–528 (2004).
Sampath, J. et al. Role of MRP4 and MRP5 in biology and chemotherapy. AAPS PharmSci [online], < http://www.aapsj.org/view.asp?art=ps040314 > (2002).
Staud, F. & Pavek, P. Breast cancer resistance protein (BCRP/ABCG2). Int. J. Biochem. Cell Biol. 37, 720–725 (2005).
Han, B. & Zhang, J. T. Multidrug resistance in cancer chemotherapy and xenobiotic protection mediated by the half ATP-binding cassette transporter ABCG2. Curr. Med. Chem. Anti-Canc. Agents 4, 31–42 (2004).
Litman, T. et al. The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2). J. Cell Sci. 113 (Pt 11), 2011–2021 (2000).
Kool, M. et al. MRP3, an organic anion transporter able to transport anti-cancer drugs. Proc. Natl Acad. Sci. USA 96, 6914–6919 (1999).
Zelcer, N., Saeki, T., Reid, G., Beijnen, J. H. & Borst, P. Characterization of drug transport by the human multidrug resistance protein 3 (ABCC3). J. Biol. Chem. 276, 46400–46407 (2001).
Wielinga, P. et al. The human multidrug resistance protein MRP5 transports folates and can mediate cellular resistance against antifolates. Cancer Res. 65, 4425–4430 (2005).
Pratt, S. et al. The multidrug resistance protein 5 (ABCC5) confers resistance to 5-fluorouracil and transports its monophosphorylated metabolites. Mol. Cancer Ther. 4, 855–863 (2005).
Wang, X. et al. Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Mol. Pharmacol. 63, 65–72 (2003).
Haimeur, A., Conseil, G., Deeley, R. G. & Cole, S. P. Mutations of charged amino acids in or near the transmembrane helices of the second membrane spanning domain differentially affect the substrate specificity and transport activity of the multidrug resistance protein MRP1 (ABCC1). Mol. Pharmacol. 65, 1375–1385 (2004).
Bradshaw, D. M. & Arceci, R. J. Clinical relevance of transmembrane drug efflux as a mechanism of multidrug resistance. J. Clin. Oncol. 16, 3674–3690 (1998).
Vastag, B. Almost serendipity: alcoholism drug reverses drug resistance in vitro. J. Natl Cancer Inst. 92, 864–865 (2000).
Evers, R. et al. Inhibitory effect of the reversal agents V-104, GF120918 and Pluronic L61 on MDR1 Pgp-, MRP1- and MRP2-mediated transport. Br. J. Cancer 83, 366–374 (2000).
Robey, R. W. et al. Pheophorbide A is a specific probe for ABCG2 function and inhibition. Cancer Res. 64, 1242–1246 (2004).
Dantzig, A. H. et al. Evaluation of the binding of the tricyclic isoxazole photoaffinity label LY475776 to multidrug resistance associated protein 1 (MRP1) orthologs and several ATP- binding cassette (ABC) drug transporters. Biochem. Pharmacol. 67, 1111–1121 (2004).
Shepard, R. L., Cao, J., Starling, J. J. & Dantzig, A. H. Modulation of P-glycoprotein but not MRP1- or BCRP-mediated drug resistance by LY335979. Int. J. Cancer 103, 121–125 (2003).
van Zuylen, L. et al. The orally administered P-glycoprotein inhibitor R101933 does not alter the plasma pharmacokinetics of docetaxel. Clin. Cancer Res. 6, 1365–1371 (2000).
Martin, C. et al. The molecular interaction of the high affinity reversal agent XR9576 with P-glycoprotein. Br. J. Pharmacol. 128, 403–411 (1999).
Hofmann, J. et al. Reversal of multidrug resistance by B859–35, a metabolite of B859–35, niguldipine, verapamil and nitrendipine. J. Cancer Res. Clin. Oncol. 118, 361–366 (1992).
Norman, B. H. et al. Cyclohexyl-linked tricyclic isoxazoles are potent and selective modulators of the multidrug resistance protein (MRP1). Bioorg. Med. Chem. Lett. 15, 5526–5530 (2005).
Wishart, G. C. et al. Quinidine as a resistance modulator of epirubicin in advanced breast cancer: mature results of a placebo-controlled randomized trial. J. Clin. Oncol. 12, 1771–1777 (1994).
Millward, M. J. et al. Oral verapamil with chemotherapy for advanced non-small cell lung cancer: a randomised study. Br. J. Cancer 67, 1031–1035 (1993).
Milroy, R. A randomised clinical study of verapamil in addition to combination chemotherapy in small cell lung cancer. West of Scotland Lung Cancer Research Group, and the Aberdeen Oncology Group. Br. J. Cancer 68, 813–818 (1993).
Dalton, W. S. et al. A phase III randomized study of oral verapamil as a chemosensitizer to reverse drug resistance in patients with refractory myeloma. A Southwest Oncology Group study. Cancer 75, 815–820 (1995).
Wood, L. et al. Results of a phase III, double-blind, placebo-controlled trial of megestrol acetate modulation of P-glycoprotein-mediated drug resistance in the first-line management of small-cell lung carcinoma. Br. J. Cancer 77, 627–631 (1998).
Liu Yin, J. A., Wheatley, K., Rees, J. K. & Burnett, A. K. Comparison of 'sequential' versus 'standard' chemotherapy as re-induction treatment, with or without cyclosporine, in refractory/relapsed acute myeloid leukaemia (AML): results of the UK Medical Research Council AML-R trial. Br. J. Haematol. 113, 713–726 (2001).
van der Holt, B. et al. 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, 2646–2654 (2005).
Wattel, E. et al. Quinine improves the results of intensive chemotherapy in myelodysplastic syndromes expressing P glycoprotein: results of a randomized study. Br. J. Haematol. 102, 1015–1024 (1998).
Sonneveld, P. et al. Cyclosporin A combined with vincristine, doxorubicin and dexamethasone (VAD) compared with VAD alone in patients with advanced refractory multiple myeloma: an EORTC-HOVON randomized phase III study (06914). Br. J. Haematol. 115, 895–902 (2001).
Solary, E. et al. Combination of quinine as a potential reversing agent with mitoxantrone and cytarabine for the treatment of acute leukemias: a randomized multicenter study. Blood 88, 1198–1205 (1996).
Solary, E. et al. Quinine as a multidrug resistance inhibitor: a phase 3 multicentric randomized study in adult de novo acute myelogenous leukemia. Blood 102, 1202–1210 (2003).
Robert, J. MS-209 Schering. Curr. Opin. Investig. Drugs 5, 1340–1347 (2004).
Joly, F. J. C. et al. A phase 3 study of PSC 833 in combination with paclitaxel and carboplatin (PC-PSC) versus paclitaxel and carboplatin (PC) alone in patients with stage IV or suboptimally debulked stage III epithelial ovarian cancer or primary cancer of the peritoneum. Proc. Am. Soc. Clin. Oncol. 21, Abstract 806 (2002).
Belpomme, D. et al. Verapamil increases the survival of patients with anthracycline-resistant metastatic breast carcinoma. Ann. Oncol. 11, 1471–1476 (2000).
Greenberg, P. L. et al. 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, 1078–1086 (2004).
Cooray, H. C. et al. Localisation of breast cancer resistance protein in microvessel endothelium of human brain. Neuroreport 13, 2059–2063 (2002).
Keppler, D. & Konig, J. Hepatic secretion of conjugated drugs and endogenous substances. Semin. Liver Dis. 20, 265–272 (2000).
Consoli, U. et al. Cellular pharmacology of mitoxantrone in p-glycoprotein-positive and-negative human myeloid leukemic cell lines. Leukemia 11, 2066–2074 (1997).
Morrow, C. S. et al. Multidrug resistance protein 1 (MRP1, ABCC1) mediates resistance to mitoxantrone via glutathione-dependent drug efflux. Mol. Pharmacol. 24 Jan 2006 [epubd ahead of print].
Williams, G. C., Liu, A., Knipp, G. & Sinko, P. J. Direct evidence that saquinavir is transported by multidrug resistance-associated protein (MRP1) and canalicular multispecific organic anion transporter (MRP2). Antimicrob. Agents Chemother. 46, 3456–3462 (2002).
Chen, Z. S. et al. Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system. Cancer Res. 62, 3144–3150 (2002).
Reid, G. et al. Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5. Mol. Pharmacol. 63, 1094–1103 (2003)
Allen, J. D., Van Dort, S. C., Buitelaar, M., van Tellingen, O. & Schinkel, A. H. Mouse breast cancer resistance protein (Bcrp1/Abcg2) mediates etoposide resistance and transport, but etoposide oral availability is limited primarily by P-glycoprotein. Cancer Res. 63, 1339–1344 (2003)
Robey, R. W. et al. Overexpression of the ATP-binding cassette half-transporter, ABCG2 (Mxr/BCrp/ABCP1), in flavopiridol-resistant human breast cancer cells. Clin. Cancer Res. 7, 145–152 (2001).
Volk, E. L. et al. Overexpression of wild-type breast cancer resistance protein mediates methotrexate resistance. Cancer Res. 62, 5035–5040 (2002).
Hyafil, F., Vergely, C., Du Vignaud, P. & Grand-Perret, T. In vitro and in vivo reversal of multidrug resistance by GF120918, an acridonecarboxamide derivative. Cancer Res. 53, 4595–4602 (1993).
Venne, A., Li, S., Mandeville, R., Kabanov, A. & Alakhov, V. Hypersensitizing effect of pluronic L61 on cytotoxic activity, transport, and subcellular distribution of doxorubicin in multiple drug-resistant cells. Cancer Res. 56, 3626–3629 (1996).
Germann, U. A., Ford, P. J., Shlyakhter, D., Mason, V. S. & Harding, M. W. Chemosensitization and drug accumulation effects of VX-710, verapamil, cyclosporin A, MS-209 and GF120918 in multidrug resistant HL60/ADR cells expressing the multidrug resistance-associated protein MRP. Anticancer Drugs 8, 141–155 (1997).
Sauna, Z. E., Peng, X. H., Nandigama, K., Tekle, S. & Ambudkar, S. V. The molecular basis of the action of disulfiram as a modulator of the multidrug resistance-linked ATP binding cassette transporters MDR1 (ABCB1) and MRP1 (ABCC1). Mol. Pharmacol. 65, 675–684 (2004).
Chen, Z. S. et al. Effect of multidrug resistance-reversing agents on transporting activity of human canalicular multispecific organic anion transporter. Mol. Pharmacol. 56, 1219–1228 (1999).
Qadir, M. et al. Cyclosporin A is a broad-spectrum multidrug resistance modulator. Clin. Cancer Res. 11, 2320–2326 (2005).
de Bruin, M., Miyake, K., Litman, T., Robey, R. & Bates, S. E. Reversal of resistance by GF120918 in cell lines expressing the ABC half-transporter, MXR. Cancer Lett. 146, 117–126 (1999).
Rabindran, S. K., Ross, D. D., Doyle, L. A., Yang, W. & Greenberger, L. M. Fumitremorgin C reverses multidrug resistance in cells transfected with the breast cancer resistance protein. Cancer Res. 60, 47–50 (2000).
Lecureur, V. et al. Cloning and expression of murine sister of P-glycoprotein reveals a more discriminating transporter than MDR1/P-glycoprotein. Mol. Pharmacol. 57, 24–35 (2000).