Multidrug resistance in cancer: role of ATP–dependent transporters (original) (raw)

• Gorre, M. E. et al. Clinical resistance to STI-571 cancer therapy caused by BCR–ABL gene mutation or amplification. Science 293, 876–880 (2001).
  Article CAS PubMed Google Scholar
• Pluen, A. et al. Role of tumor–host interactions in interstitial diffusion of macromolecules: cranial vs. subcutaneous tumors. Proc. Natl Acad. Sci. USA 98, 4628–4633 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Jain, R. K. Delivery of molecular and cellular medicine to solid tumors. Adv. Drug Deliv. Rev. 46, 149–168 (2001).
  Article CAS PubMed Google Scholar
• Jain, R. K. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nature Med. 7, 987–989 (2001).
  Article CAS PubMed Google Scholar
• Green, S. K., Frankel, A. & Kerbel, R. S. Adhesion-dependent multicellular drug resistance. Anticancer Drug Des. 14, 153–168 (1999).
  CAS PubMed Google Scholar
• Durand, R. E. & Olive, P. L. Resistance of tumor cells to chemo- and radiotherapy modulated by the three-dimensional architecture of solid tumors and spheroids. Methods Cell Biol. 64, 211–233 (2001).
  Article CAS PubMed Google Scholar
• Dean, M., Rzhetsky, A. & Alliknets, R. The human ATP-binding cassette (ABC) transporter superfamily. Genome Res. 11, 1156–1166 (2001).Most recent update of the ABC transporter family, emphasizing genetic disorders that result from disruption of ABC genes.
  Article CAS PubMed Google Scholar
• Ambudkar, S. V. et al. Biochemical, cellular, and pharmacological aspects of the multidrug transporter. Annu. Rev. Pharmacol. Toxicol. 39, 361–398 (1999).
  Article CAS PubMed Google Scholar
• Shen, D. W., Goldenberg, S., Pastan, I. & Gottesman, M. M. Decreased accumulation of [14C]carboplatin in human cisplatin-resistant cells results from reduced energy-dependent uptake. J. Cell Physiol. 183, 108–116 (2000).
  Article CAS PubMed Google Scholar
• Shen, D., Pastan, I. & Gottesman, M. M. Cross-resistance to methotrexate and metals in human cisplatin-resistant cell lines results from a pleiotropic defect in accumulation of these compounds associated with reduced plasma membrane binding proteins. Cancer Res. 58, 268–275 (1998).
  CAS PubMed Google Scholar
• Schuetz, E. G., Beck, W. T. & Schuetz, J. D. Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells. Mol. Pharmacol. 49, 311–318 (1996).
  CAS PubMed Google Scholar
• 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).This paper provides direct evidence for coordination of drug-detoxifying systems through activation of a single transcription factor, SXR.
  Article CAS PubMed Google Scholar
• Liu, Y. Y., Han, T. Y., Giuliano, A. E. & Cabot, M. C. Ceramide glycosylation potentiates cellular multidrug resistance. FASEB J. 15, 719–730 (2001).
  Article CAS PubMed Google Scholar
• Juliano, R.L. & Ling, V. A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim. Biophys. Acta 455, 152–162 (1976).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• Chen, C.J. et al. Internal duplication and homology with bacterial transport proteins in _Mdr_-1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell 47, 371–380 (1986).Description of the sequence of the MDR1 (P-glycoprotein) cDNA and its homology to two bacterial transporters, thereby defining the first members of the ABC transporter family.
  Article Google Scholar
• Senior, A. E. & Bhagat, S. P-glycoprotein shows strong catalytic cooperativity between the two nucleotide sites. Biochemistry 37, 831–836 (1998).
  Article CAS PubMed Google Scholar
• Ramachandra, M. et al. Human P-glycoprotein exhibits reduced affinity for substrates during a catalytic transition state. Biochemistry 37, 5010–5019 (1998).
  Article CAS PubMed Google Scholar
• Sauna, Z. E. & Ambudkar, S. V. Evidence for a requirement for ATP hydrolysis at two distinct steps during a single turnover of the catalytic cycle of human P-glycoprotein. Proc. Natl Acad. Sci. USA 97, 2515–2520 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Cole, S.P.C. et al. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science 258, 1650–1654 (1992).
  Article CAS PubMed Google Scholar
• Loe, D. W., Deeley, R. G. & Cole, S. P. Characterization of vincristine transport by the M(r) 190,000 multidrug resistance protein (MRP): evidence for cotransport with reduced glutathione. Cancer Res. 58, 5130–5136 (1998).
  CAS PubMed Google Scholar
• Jedlitschky, G. et al. Transport of glutathione, glucuronate, and sulfate conjugates by the MRP gene-encoded conjugate export pump. Cancer Res. 56, 988–994 (1996).Observations that led to the conclusion that MRP was a broad-specificity organic anion transporter.
  CAS PubMed Google Scholar
• Muller, M. et al. Overexpression of the gene encoding the multidrug resistance-associated protein results in increased ATP-dependent glutathione S-conjugate transport. Proc. Natl Acad. Sci. USA 91, 13033–13037 (1994).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  CAS PubMed Google Scholar
• Honjo, Y. et al. Acquired mutations in the MXR/BCRP/ABCP gene alter substrate specificity in MXR/BCRP/ABCP-overexpressing cells. Cancer Res. (in the press).
• Komatani, H. et al. Identification of breast cancer resistant protein/mitoxantrone resistance/placenta-specific, ATP-binding cassette transporter as a transporter of NB-506 and J-107088, topoisomerase I inhibitors with an indolocarbazole structure. Cancer Res. 61, 2827–2832 (2001).
  CAS PubMed Google Scholar
• 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).
  CAS PubMed Google Scholar
• Smit, J. J. et al. Homozygous disruption of the murine Mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. Cell 75, 451–462 (1993).
  Article CAS PubMed Google Scholar
• Zhou, Y., Gottesman, M. M. & Pastan, I. Studies of human MDR1–MDR2 chimeras demonstrate the functional exchangeability of a major transmembrane segment of the multidrug transporter and phosphatidylcholine flippase. Mol. Cell Biol. 19, 1450–1459 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Borst, P., Zelcer, N. & van Helvoort, A. ABC transporters in lipid transport. Biochim. Biophys. Acta 1486, 128–144 (2000).
  Article CAS PubMed Google Scholar
• 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).
  CAS PubMed Google Scholar
• 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).
  CAS PubMed Google Scholar
• Scheffer, G. L., Schroeijers, A. B., Izquierdo, M. A., Wiemer, E. A. & Scheper, R. J. Lung resistance-related protein/major vault protein and vaults in multidrug-resistant cancer. Curr. Opin. Oncol. 12, 550–556 (2000).
  Article CAS PubMed Google Scholar
• Kool, M. et al. MRP3, an organic anion transporter able to transport anti-cancer drugs. Proc. Natl Acad. Sci. USA 96, 6914–6919 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Belinsky, M. G. & Kruh, G. D. MOAT-E (ARA) is a full-length MRP/cMOAT subfamily transporter expressed in kidney and liver. Br. J. Cancer 80, 1342–1349 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Schuetz, J. D. et al. MRP4: a previously unidentified factor in resistance to nucleoside-based antiviral drugs. Nature Med. 5, 1048–1051 (1999).
  Article CAS PubMed Google Scholar
• Wijnholds, J. et al. Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs. Proc. Natl Acad. Sci. USA 97, 7476–7481 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Jedlitschky, G., Burchell, B. & Keppler, D. The multidrug resistance protein 5 functions as an ATP-dependent export pump for cyclic nucleotides. J. Biol. Chem. 275, 30069–30074 (2000).
  Article CAS PubMed Google Scholar
• Struk, B. et al. Mutations of the gene encoding the transmembrane transporter protein ABC-C6 cause pseudoxanthoma elasticum. J. Mol. Med. 78, 282–286 (2000).
  Article CAS PubMed Google Scholar
• Bergen, A. A. et al. Mutations in ABCC6 cause pseudoxanthoma elasticum. Nature Genet. 25, 228–231 (2000).
  Article CAS PubMed Google Scholar
• Ringpfeil, F., Lebwohl, M. G., Christiano, A. M. & Uitto, J. Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter. Proc. Natl Acad. Sci. USA 97, 6001–6006 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Le Saux, O. et al. Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum. Nature Genet. 25, 223–227 (2000).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  CAS PubMed Google Scholar
• Schinkel, A. H., Wagenaar, E., Mol, C. A. & van Deemter, L. P-glycoprotein in the blood–brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J. Clin. Invest. 97, 2517–2524 (1996).Follow-up study to the landmark observation that disruption of the PGPs failed to evoke a disease phenotype, but did render mice extraordinarily sensitive to ivermectin. This implicated a role for PGP in the blood–brain barrier.
  Article CAS PubMed PubMed Central Google Scholar
• Xie, R., Hammarlund-Udenaes, M., de Boer, A. G. & de Lange, E. C. The role of P-glycoprotein in blood–brain barrier transport of morphine: transcortical microdialysis studies in Mdr1a (−/−) and Mdr1a (+/+) mice. Br. J. Pharmacol. 128, 563–568 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• 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).Description of MRP and PGP localization in the epithelium of choroid plexus, and prediction of distinctive roles in the blood–cerebrospinal-fluid barrier.
  Article CAS PubMed PubMed Central Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• 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).
  CAS PubMed Google Scholar
• St-Pierre, M. V. et al. Expression of members of the multidrug resistance protein family in human term placenta. Am. J. Physiol. 279, R1495–R1503 (2000). | PubMed |
  Article CAS Google Scholar
• Schinkel, A. H. et al. Normal viability and altered pharmacokinetics in mice lacking Mdr1-type (drug-transporting) P-glycoproteins. Proc. Natl Acad. Sci. USA 94, 4028–4033 (1997).Clear demonstration that PGP affects the tissue distribution and retention of drugs other than anticancer agents.
  Article CAS PubMed PubMed Central Google Scholar
• Scheffer, G. L. et al. Specific detection of multidrug resistance proteins MRP1, MRP2, MRP3, MRP5, and MDR3 P-glycoprotein with a panel of monoclonal antibodies. Cancer Res. 60, 5269–5277 (2000).
  CAS PubMed Google Scholar
• Kool, M., van der Linden, M., de Haas, M., Baas, F. & Borst, P. Expression of human MRP6, a homologue of the multidrug resistance protein gene MRP1, in tissues and cancer cells. Cancer Res. 59, 175–182 (1999).
  CAS PubMed Google Scholar
• Konig, J., Nies, A. T., Cui, Y., Leier, I. & Keppler, D. Conjugate export pumps of the multidrug resistance protein (MRP) family: localization, substrate specificity, and MRP2-mediated drug resistance. Biochim. Biophys. Acta 1461, 377–394 (1999).
  Article CAS PubMed Google Scholar
• Paulusma, C. C. et al. Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene. Science 271, 1126–1128 (1996).
  Article CAS PubMed Google Scholar
• Ito, K. et al. Molecular cloning of canalicular multispecific organic anion transporter defective in EHBR. Am. J. Physiol. 272, G16–G22 (1997).
  CAS PubMed Google Scholar
• Kartenbeck, J., Leuschner, U., Mayer, R. & Keppler, D. Absence of the canalicular isoform of the MRP gene-encoded conjugate export pump from the hepatocytes in Dubin–Johnson syndrome. Hepatology 23, 1061–1066 (1996).
  CAS PubMed Google Scholar
• Paulusma, C. C. et al. A mutation in the human canalicular multispecific organic anion transporter gene causes the Dubin–Johnson syndrome. Hepatology 25, 1539–1542 (1997).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Wang, R. et al. Targeted inactivation of sister of P-glycoprotein gene (Spgp) in mice results in nonprogressive but persistent intrahepatic cholestasis. Proc. Natl Acad. Sci. USA 98, 2011–2016 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Ruetz, S. & Gros, P. Phosphatidylcholine translocase: a physiological role for the Mdr2 gene. Cell 77, 1071–1081 (1994).First physiological role for an MDR gene is convincingly described.
  Article CAS PubMed Google Scholar
• de Vree, J. M. et al. Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis. Proc. Natl Acad. Sci. USA 95, 282–287 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Mayer, U. et al. Full blockage of intestinal P-glycoprotein and extensive inhibition of blood–brain barrier P-glycoprotein by oral treatment of mice with PSC-833. J. Clin. Invest. 100, 2430–2436 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Greiner, B. et al. The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. J. Clin. Invest. 104, 147–153 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Lown, K. S. et al. Role of intestinal P-glycoprotein (Mdr1) in interpatient variation in the oral bioavailability of cyclosporine. Clin. Pharmacol. Ther. 62, 248–260 (1997).
  Article CAS PubMed Google Scholar
• Sparreboom, A. et al. Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc. Natl Acad. Sci. USA 94, 2031–2035 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Evers, R. et al. Basolateral localization and export activity of the human multidrug resistance-associated protein in polarized pig kidney cells. J. Clin. Invest. 97, 1211–1218 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Wijnholds, J. et al. Increased sensitivity to anticancer drugs and decreased inflammatory response in mice lacking the multidrug resistance-associated protein. Nature Med. 3, 1275–1279 (1997).
  Article CAS PubMed Google Scholar
• Dietrich, C. G., de Waart, D. R., Ottenhoff, R., Schoots, I. G. & Elferink, R. P. Increased bioavailability of the food-derived carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-_b_] pyridine in Mrp2-deficient rats. Mol. Pharmacol. 59, 974–980 (2001).
  Article CAS PubMed Google Scholar
• Fojo, A.T. et al. Expression of a multidrug resistance gene in human tumors and tissues. Proc. Natl Acad. Sci. USA 84, 265–269 (1987).
  Article CAS PubMed PubMed Central Google Scholar
• Goldstein, L. J. et al. Expression of a multidrug resistance gene in human cancers. J. Natl Cancer Inst. 81, 116–124 (1989).
  Article CAS PubMed Google Scholar
• van den Heuvel-Eibrink, M. M., Sonneveld, P. & Pieters, R. The prognostic significance of membrane transport-associated multidrug resistance (MDR) proteins in leukemia. Int. J. Clin. Pharmacol. Ther. 38, 94–110 (2000).
  Article CAS PubMed Google Scholar
• Beck, W.T. et al. Methods to detect P-glycoprotein-associated multidrug resistance in patients' tumors: consensus recommendations. Cancer Res. 56, 3010–3020 (1996).
  CAS PubMed Google Scholar
• Hipfner, D. R. et al. Epitope mapping of monoclonal antibodies specific for the 190-kDa multidrug resistance protein (MRP). Br. J. Cancer 78, 1134–1140 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Nooter, K. et al. Expression of the multidrug resistance-associated protein (MRP) gene in human cancers. Clin. Cancer Res. 1, 1301–1310 (1995).
  CAS PubMed Google Scholar
• 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).Assay of leukaemic cells obtained from 351 patients with acute myelogenous leukaemia, and confirmation that PGP expression and function correlate with a decreased complete remission rate and an increased rate of resistant disease.
  CAS PubMed Google Scholar
• Han, K. et al. Expression of functional markers in acute nonlymphoblastic leukemia. Acta Haematol. 104, 174–180 (2000).
  Article CAS PubMed Google Scholar
• Dorr, R. et al. Phase I/II study of the P-glycoprotein modulator PSC 833 in patients with acute myeloid leukemia. J. Clin. Oncol. 19, 1589–1599 (2001).
  Article CAS PubMed Google Scholar
• van der Kolk, D. M. et al. P-glycoprotein and multidrug resistance protein activities in relation to treatment outcome in acute myeloid leukemia. Clin. Cancer Res. 6, 3205–3214 (2000).
  CAS PubMed Google Scholar
• Legrand, O., Simonin, G., Beauchamp-Nicoud, A., Zittoun, R. & Marie, J. P. Simultaneous activity of MRP1 and PGP is correlated with in vitro resistance to daunorubicin and with in vivo resistance in adult acute myeloid leukemia. Blood 94, 1046–1056 (1999).
  Article CAS PubMed Google Scholar
• Michieli, M. et al. P-glycoprotein, lung resistance-related protein and multidrug resistance associated protein in de novo acute non-lymphocytic leukaemias: biological and clinical implications. Br. J. Haematol. 104, 328–335 (1999).
  Article CAS PubMed Google Scholar
• Broxterman, H. J. et al. Do P-glycoprotein and major vault protein (MVP/LRP) expression correlate with in vitro daunorubicin resistance in acute myeloid leukemia? Leukemia 13, 258–265 (1999).
  Article CAS PubMed Google Scholar
• Tidefelt, U. et al. 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, 1837–1844 (2000).
  Article CAS PubMed Google Scholar
• Burger, H. et al. Expression of the multidrug resistance-associated protein (MRP) in acute and chronic leukemias. Leukemia 8, 990–997 (1994).
  CAS PubMed Google Scholar
• Filipits, M. et al. Multidrug resistance-associated protein in acute myeloid leukemia: no impact on treatment outcome. Clin. Cancer Res. 3, 1419–1425 (1997).
  CAS PubMed Google Scholar
• Ross, D. D., Karp, J. E., Chen, T. T. & Doyle, L. A. Expression of breast cancer resistance protein in blast cells from patients with acute leukemia. Blood 96, 365–368 (2000).
  Article CAS PubMed Google Scholar
• 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).Meta-analysis showing PGP expression in approximately 40% of breast cancer samples, and a correlation with decreased treatment response.
  Article CAS PubMed Google Scholar
• Vecchio, S. D. et al. In vivo detection of multidrug-resistant (MDR1) phenotype by 99m sestamibi scan in untreated breast cancer patients. Eur. J. Nucl. Med. 24, 150–159 (1997).Study showing an inverse correlation between MRK-16 binding to breast cancer samples and 99m Tc-sestamibi retention in breast cancers.
  Article CAS PubMed Google Scholar
• Sun, S. S. et al. Expression of mediated P-glycoprotein multidrug resistance related to Tc-99m MIBI scintimammography results. Cancer Lett. 153, 95–100 (2000).
  Article CAS PubMed Google Scholar
• Kao, C. H. et al. P-glycoprotein and multidrug resistance-related protein expressions in relation to technetium-99m methoxyisobutylisonitrile scintimammography findings. Cancer Res. 61, 1412–1414 (2001).
  CAS PubMed Google Scholar
• Dexter, D. W. et al. Quantitative reverse transcriptase-polymerase chain reaction measured expression of MDR1 and MRP in primary breast carcinoma. Clin. Cancer Res. 4, 1533–1542 (1998).
  CAS PubMed Google Scholar
• Filipits, M. et al. MRP and MDR1 gene expression in primary breast carcinomas. Clin. Cancer Res. 2, 1231–1237 (1996).
  CAS PubMed Google Scholar
• Nooter, K. et al. The prognostic significance of expression of the multidrug resistance-associated protein (MRP) in primary breast cancer. Br. J. Cancer 76, 486–493 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Oka, M. et al. The clinical role of MDR1 gene expression in human lung cancer. Anticancer Res. 17, 721–724 (1997).
  CAS PubMed Google Scholar
• Savaraj, N. et al. Multidrug-resistant gene expression in small-cell lung cancer. Am. J. Clin. Oncol. 20, 398–403 (1997).
  Article CAS PubMed Google Scholar
• Young, L. C. et al. Expression of multidrug resistance protein-related genes in lung cancer: correlation with drug response. Clin. Cancer Res. 5, 673–680 (1999).
  CAS PubMed Google Scholar
• Nooter, K. et al. Expression of the multidrug resistance-associated protein (MRP) gene in primary non-small-cell lung cancer. Ann. Oncol. 7, 75–81 (1996).
  Article CAS PubMed Google Scholar
• Wright, S. R. et al. Immunohistochemical detection of multidrug resistance protein in human lung cancer and normal lung. Clin. Cancer Res. 4, 2279–2289 (1998).
  CAS PubMed Google Scholar
• Chan, H. S. L., Thorner, P. S., Haddad, G. & Ling, V. Immunohistochemical detection of P-glycoprotein: prognostic correlation in soft tissue sarcoma of childhood. J. Clin. Oncol. 8, 689–704 (1990).
  Article CAS PubMed Google Scholar
• Chan, H. S., Grogan, T. M., Haddad, G., DeBoer, G. & Ling, V. P-glycoprotein expression: critical determinant in the response to osteosarcoma chemotherapy. J. Natl Cancer Inst. 89, 1706–1715 (1997).
  Article CAS PubMed Google Scholar
• Perri, T. et al. Effect of P-glycoprotein expression on outcome in the Ewing family of tumors. Pediatr. Hematol. Oncol. 18, 325–334 (2001).
  Article CAS PubMed Google Scholar
• Baldini, N. et al. Expression of P-glycoprotein in high-grade osteosarcomas in relation to clinical outcome. N. Engl. J. Med. 333, 1380–1385 (1995).
  Article CAS PubMed Google Scholar
• Coley, H. M. et al. Incidence of P-glycoprotein overexpression and multidrug resistance (MDR) reversal in adult soft tissue sarcoma. Eur. J. Cancer 36, 881–888 (2000).
  Article CAS PubMed Google Scholar
• Wunder, J. S. et al. MDR1 gene expression and outcome in osteosarcoma: a prospective, multicenter study. J. Clin. Oncol. 18, 2685–2694 (2000).
  Article CAS PubMed Google Scholar
• Kuttesch, J. F. et al. P-glycoprotein expression at diagnosis may not be a primary mechanism of therapeutic failure in childhood rhabdomyosarcoma. J. Clin. Oncol. 14, 886–900 (1996).
  Article CAS PubMed Google Scholar
• Ferry, D. R., Traunecker, H. & Kerr, D. J. Clinical trials of P-glycoprotein reversal in solid tumours. Eur. J. Cancer 32A, 1070–1081 (1996).
  Article CAS PubMed Google Scholar
• Kerr, D. J. et al. The effect of verapamil on the pharmacokinetics of adriamycin. Cancer Chemother. Pharmacol. 18, 239–242 (1986).
  Article CAS PubMed Google Scholar
• Fisher, G. A. & Sikic, B. I. Clinical studies with modulators of multidrug resistance. Hematol Oncol Clin North Am 9, 363–382 (1995).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Fisher, G. A., Lum, B. L., Hausdorff, J. & Sikic, B. I. Pharmacological considerations in the modulation of multidrug resistance. Eur. J. Cancer 32A, 1082–1088 (1996).
  Article CAS PubMed Google Scholar
• Chaudhary, P. M. & Roninson, I. B. Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells. Cell 66, 85–94 (1991).Early paper that highlights the role of P-glycoprotein in normal cells.
  Article CAS PubMed Google Scholar
• Chico, I. et al. Phase I study of infusional paclitaxel in combination with the P-glycoprotein antagonist PSC- 833. J. Clin. Oncol. 19, 832–842 (2001).
  Article CAS PubMed Google Scholar
• Advani, R. et al. Treatment of refractory and relapsed acute myelogenous leukemia with combination chemotherapy plus the multidrug resistance modulator PSC-833 (Valspodar). Blood 93, 787–795 (1999).
  Article CAS PubMed Google Scholar
• Kornblau, S. M. et al. Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia. J. Clin. Oncol. 15, 1796–1802 (1997).
  Article CAS PubMed Google Scholar
• List, A. F. et al. Phase I/II trial of cyclosporine as a chemotherapy-resistance modifier in acute leukemia. J. Clin. Oncol. 11, 1652–1660 (1993).
  Article CAS PubMed Google Scholar
• Lee, E. J. et al. Parallel phase I studies of daunorubicin given with cytarabine and etoposide with or without the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age or older with acute myeloid leukemia: results of cancer and leukemia group B study 9420. J. Clin. Oncol. 17, 2831–2839 (1999).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• List, A. F. et al. Benefit of cyclosporine (CsA) modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group (SWOG) Study. Blood 98, 3212–3220 (2001).These long-term results indicate a survival advantage of treatment of acute myelogenous leukaemia with daunomycin in combination with the PGP antagonist cyclosporin A.
  Article CAS PubMed Google Scholar
• Sonneveld, P. et al. Modulation of multidrug-resistant multiple myeloma by cyclosporin. Lancet 340, 255–259 (1992).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed PubMed Central Google Scholar
• Fracasso, P. M. et al. Phase I study of paclitaxel in combination with a multidrug resistance modulator, PSC-833 (Valspodar), in refractory malignancies. J. Clin. Oncol. 18, 1124 (2000).
  Article CAS PubMed Google Scholar
• Fracasso, P. M. et al. Phase II study of paclitaxel and valspodar (PSC-833) in refractory ovarian carcinoma: a gynecologic oncology group study. J. Clin. Oncol. 19, 2975–2982 (2001).
  Article CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Lum, B. L. et al. Alteration of etoposide pharmacokinetics and pharmacodynamics by cyclosporine in a phase I trial to modulate multidrug resistance. J. Clin. Oncol. 10, 1635–1642 (1992).
  Article CAS PubMed Google Scholar
• Bartlett, N. L. et al. Phase I trial of doxorubicin with cyclosporine as a modulator of multidrug resistance. J. Clin. Oncol. 12, 835–842 (1994).
  Article CAS PubMed Google Scholar
• Rowinsky, E. K. et al. 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, 2964–2976 (1998).
  Article CAS PubMed Google Scholar
• Wilson, W. H. et al. Phase I and pharmacokinetic study of the multidrug resistance modulator dexverapamil with EPOCH chemotherapy. J. Clin. Oncol. 13, 1985–1994 (1995).
  Article CAS PubMed Google Scholar
• Sparreboom, A. et al. Clinical pharmacokinetics of doxorubicin in combination with GF120918, a potent inhibitor of MDR1 P-glycoprotein. Anticancer Drugs 10, 719–728 (1999).
  Article CAS PubMed Google Scholar
• Advani, R. et al. A phase I trial of doxorubicin, paclitaxel, and valspodar (PSC- 833), a modulator of multidrug resistance. Clin. Cancer Res. 7, 1221–1229 (2001).
  CAS PubMed Google Scholar
• Kang, M. H. et al. The P-glycoprotein antagonist PSC- 833 increases the plasma concentrations of 6α-hydroxypaclitaxel, a major metabolite of paclitaxel. Clin. Cancer Res. 7, 1610–1617 (2001).
  CAS PubMed Google Scholar
• Solary, E. et al. Sufficient levels of quinine in the serum circumvent the multidrug resistance of the human leukemic cell line K562/ADM. Cancer 68, 1714–1719 (1991).
  Article CAS PubMed Google Scholar
• Minami, H. et al. Phase I study of intravenous PSC-833 and doxorubicin: reversal of multidrug resistance. Jpn. J. Cancer Res. 92, 220–230 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Robey, R. et al. Efflux of rhodamine from CD56+ cells as a surrogate marker for reversal of P-glycoprotein-mediated drug efflux by PSC-833. Blood 93, 306–314 (1999).
  Article CAS PubMed Google Scholar
• Witherspoon, S. M. et al. Flow cytometric assay of modulation of P-glycoprotein function in whole blood by the multidrug resistance inhibitor GG918. Clin. Cancer Res. 2, 7–12 (1996).
  CAS PubMed Google Scholar
• Luker, G.D., Facasso, P.M., Dobkin, J. & Piwnica-Worms, D. Modulation of the multidrug resistance P-glycoprotein: detection with technetium-99m-sestamibi in vivo. J. Nucl. Med. 38, 369–372 (1997).Promising study showing the ability of PSC-833 to increase liver retention of 99m Tc-sestamibi as a surrogate for PGP inhibition.
  CAS PubMed Google Scholar
• Chen, C. C. et al. Detection of in vivo P-glycoprotein inhibition by PSC-833 using Tc-99m sestamibi. Clin. Cancer Res. 3, 545–552 (1997).
  CAS PubMed Google Scholar
• Peck, R. A. et al. Phase I and pharmacokinetic study of the novel MDR1 and MRP1 inhibitor biricodar administered alone and in combination with doxorubicin. J. Clin. Oncol. 19, 3130–3141 (2001).
  Article CAS PubMed Google Scholar
• Hendrikse, N. H. et al. 99mTc-sestamibi is a substrate for P-glycoprotein and the multidrug resistance-associated protein. Br. J. Cancer 77, 353–358 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Chen, W. S. et al. Effects of MDR1 and MDR3 P-glycoproteins, MRP1, and BCRP/MXR/ABCP on the transport of (99m)Tc-tetrofosmin. Biochem. Pharmacol. 60, 413–426 (2000).
  Article CAS PubMed Google Scholar
• Beketic-Oreskovic, L., Duran, G. E., Chen, G., Dumontet, C. & Sikic, B. I. Decreased mutation rate for cellular resistance to doxorubicin and suppression of Mdr1 gene activation by the cyclosporin PSC-833. J. Natl Cancer Inst. 87, 1593–1602 (1995).Cells exposed to doxorubicin in the presence of PSC-833 develop resistance less frequently, supporting an argument for early intervention with PGP inhibitors.
  Article CAS PubMed Google Scholar
• 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).
  CAS PubMed Google Scholar
• Lee, J. S. et al. Rhodamine efflux patterns predict P-glycoprotein substrates in the National Cancer Institute Drug Screen. Mol. Pharmacol. 46, 627–638 (1994).
  CAS PubMed Google Scholar
• Sorrentino, B. P. et al. Selection of drug-resistant bone marrow cells in vivo after retroviral transfer of human MDR1. Science 257, 99–103 (1992).First use of MDR1 in a gene therapy setting, providing a means to increase dose intensity by protecting bone-marrow cells from chemotherapy toxicity.
  Article CAS PubMed Google Scholar
• Flasshove, M. et al. Ex vivo expansion and selection of human CD34+ peripheral blood progenitor cells after introduction of a mutated dihydrofolate reductase cDNA via retroviral gene transfer. Blood 85, 566–574 (1995).
  Article CAS PubMed Google Scholar
• Moscow, J. A. et al. Engraftment of MDR1 and NeoR gene-transduced hematopoietic cells after breast cancer chemotherapy. Blood 94, 52–61 (1999).
  Article CAS PubMed Google Scholar
• Bunting, K. D., Galipeau, J., Topham, D., Benaim, E. & Sorrentino, B. P. Transduction of murine bone marrow cells with an MDR1 vector enables ex vivo stem cell expansion, but these expanded grafts cause a myeloproliferative syndrome in transplanted mice. Blood 92, 2269–2279 (1998).
  Article CAS PubMed Google Scholar
• Dano, K. Active outward transport of daunomycin in resistant Ehrlich ascites tumor cells. Biochim. Biophys. Acta 323, 466–483 (1973).
  Article CAS PubMed Google Scholar
• Abraham, J. et al. A phase I study of the novel P-glycoprotein (PGP) antagonist, XR9576 in combination with vinorelbine. Proc. Am. Soc. Clin. Oncol. 20, 287 (2001).
  Google Scholar
• Dantzig, A. H. et al. Reversal of P-glycoprotein-mediated multidrug resistance by a potent cyclopropyldibenzosuberane modulator, LY335979. Cancer Res. 56, 4171–4179 (1996).
  CAS PubMed Google Scholar
• Starling, J. J. et al. Pharmacological characterization of LY335979: a potent cyclopropyldibenzosuberane modulator of P-glycoprotein. Adv. Enzyme Regul. 37, 335–347 (1997).
  Article CAS PubMed Google Scholar
• 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).
  CAS PubMed Google Scholar
• 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).
  Article CAS PubMed Google Scholar
• Lowe, S. W., Ruley, H. E., Jacks, T. & Housman, D. E. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74, 957–967 (1993).
  Article CAS PubMed Google Scholar
• Schneider, J. et al. Expression of LRP and MDR1 in locally advanced breast cancer preditcs axillary node invasion at the time of rescue mastectomy after induction chemotherapy. Breast Cancer Res. 3, 183–191 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Tolcher, A. W. et al. Phase I crossover study of paclitaxel with r-verapamil in patients with metastatic breast cancer. J. Clin. Oncol. 14, 1173–1184 (1996).
  Article CAS PubMed Google Scholar
• Mechetner, E. et al. Levels of multidrug resistance (MDR1) P-glycoprotein expression by human breast cancer correclate with in vitro resistance to taxol and doxorubicin. Clin. Cancer Res. 4, 389–398 (1998).
  CAS PubMed Google Scholar
• Izquierdo, M. A. et al. Drug resistance-associated marker LRP for prediction of response to chemotherapy and prognoses in advanced ovarian carcinoma. J. Natl Cancer Inst. 87, 1230–1237 (1995).
  Article CAS PubMed Google Scholar
• Schneider, J., Jimenez, E., Marenbach, K., Marx, D. & Meden, H. Co-expression of the MDR1 gene and HSP27 in human ovarian cancer. Anticancer Res. 18, 2967–2971 (1998).
  CAS PubMed Google Scholar
• Baekelandt, M. M., Holm, R., Nesland, J. M., Troupe, C. G. & Kristensen, G. B. P-glycoprotein expression is a marker for chemotherapy resistance and prognosis in advanced ovarian cancer. Anticancer Res. 20, 1061–1067 (2000).
  CAS PubMed Google Scholar
• Fedeli, L. et al. Pharmacokinetics of vincristine in cancer patients treated with nifedipine. Cancer 64, 1805–1811 (1989).
  Article CAS PubMed Google Scholar