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SOLVING THE PROBLEM OF MULTIDRUG RESISTANCE: ABC TRANSPORTERS IN CLINICAL ONCOLOGY
Published 2003 · Biology
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Time to take this seriously.
Acquired drug resistance was first observed in a laboratory model in 1950, in mouse leukemic cells passaged in mice treated with 4-amino- N 10 -methyl-pteroylglutamic acid. Daunorubicin-selected resistant tumor cells were found to have energy-dependent transport of daunorubicin that could be inhibited by vinblastine, vincristine, and other anthracyclines. Further, selection of cells for resistance to vinblastine resulted in the same phenotype. Tumor cell lines that were selected in the laboratory for resistance to doxorubicin or vincristine became cross-resistant to structurally unrelated anticancer agents, displayed active outward drug efflux, and were characterized by increased expression of a 170 kDa cell membrane glycoprotein that became known as P170 or P-glycoprotein. As critical as this discovery of the first human ATP-binding cassette (ABC) transporter was, it was the observation that drug resistance could be reversed in vitro by several different compounds, including verapamil that brought Pgp into prominence as a potential target for improving cancer therapy. This chapter begins by reviewing the mammalian ABC transporters linked to multidrug resistance. It also reviews the progress that has been made in developing ABC transporters as clinical targets in anticancer therapy.
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The orally administered P-glycoprotein inhibitor R101933 does not alter the plasma pharmacokinetics of docetaxel.
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P-Glycoprotein inhibitor valspodar (PSC 833) increases the intracellular concentrations of daunorubicin in vivo in patients with P-glycoprotein-positive acute myeloid leukemia.
U. Tidefelt (2000)
P-glycoprotein expression is a marker for chemotherapy resistance and prognosis in advanced ovarian cancer.
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Hendrik W. van Veen (2000)
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J. Jonker (2000)
Expression of breast cancer resistance protein in blast cells from patients with acute leukemia
D. Ross (2000)
Multidrug resistance protein 1 protects the choroid plexus epithelium and contributes to the blood-cerebrospinal fluid barrier.
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J. Wijnholds (2000)
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T. Litman (2000)
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P. Borst (2000)
Expression of LRP and MDR1 in locally advanced breast cancer predicts axillary node invasion at the time of rescue mastectomy after induction chemotherapy
J. Schneider (2000)
A common pharmacophore for epothilone and taxanes: molecular basis for drug resistance conferred by tubulin mutations in human cancer cells.
Paraskevi Giannakakou (2000)
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S. Toh (2000)
P-glycoprotein in primary acute myeloid leukemia and treatment outcome of idarubicin/cytosine arabinoside-based induction therapy
H. Broxterman (2000)
Drug- and estrogen-induced cholestasis through inhibition of the hepatocellular bile salt export pump (Bsep) of rat liver.
B. Stieger (2000)
Expression of Functional Markers in Acute Nonlymphoblastic Leukemia
Kyungja Han (2000)
Comparative study of Tc-99m MIBI and TI-201 SPECT in predicting chemotherapeutic response in non-small-cell lung cancer.
Y. Nishiyama (2000)
Phase I Study of Intravenous PSC‐833 and Doxorubicin: Reversal of Multidrug Resistance
H. Minami (2001)
Multidrug resistance proteins MRP3, MRP1, and MRP2 in lung cancer: correlation of protein levels with drug response and messenger RNA levels.
L. C. Young (2001)
A phase I trial of doxorubicin, paclitaxel, and valspodar (PSC 833), a modulator of multidrug resistance.
R. Advani (2001)
The human ATP-binding cassette (ABC) transporter superfamily.
M. Dean (2001)
Phase I study of infusional paclitaxel in combination with the P-glycoprotein antagonist PSC 833.
I. Chico (2001)
In vitro and in vivo reversal of P-glycoprotein-mediated multidrug resistance by a novel potent modulator, XR9576.
P. Mistry (2001)
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Z. Chen (2001)
Acquired mutations in the MXR/BCRP/ABCP gene alter substrate specificity in MXR/BCRP/ABCP-overexpressing cells.
Yasumasa Honjo (2001)
Expression of Multidrug Resistance‐related Transporters in Human Breast Carcinoma
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Phase I/II trial of the multidrug-resistance modulator valspodar combined with cisplatin and doxorubicin in refractory ovarian cancer.
M. Baekelandt (2001)
Toxicological relevance of the multidrug resistance protein 1, MRP1 (ABCC1) and related transporters.
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M. Maliepaard (2001)
Phase I and pharmacokinetic study of the novel MDR1 and MRP1 inhibitor biricodar administered alone and in combination with doxorubicin.
R. Peck (2001)
Targeted inactivation of sister of P-glycoprotein gene (spgp) in mice results in nonprogressive but persistent intrahepatic cholestasis.
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Characterization of the Catalytic Cycle of ATP Hydrolysis by Human P-glycoprotein
Z. Sauna (2001)
Evaluation of chemotherapy response using technetium‐99M‐sestamibi scintigraphy in untreated adult malignant lymphomas and comparison with other prognosis factors: A preliminary report
C. Kao (2001)
Combined action of PSC 833 (Valspodar), a novel MDR reversing agent, with mitoxantrone, etoposide and cytarabine in poor-prognosis acute myeloid leukemia
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