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Blood, 1 November 2004, Vol. 104, No. 9, pp. 2940-2942. Prepublished online as a Blood First Edition Paper on July 13, 2004; DOI 10.1182/blood-2004-04-1398. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1398v1 104/9/2940    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Burger, H. Articles by Nooter, K. Search for Related Content PubMed PubMed Citation Articles by Burger, H. Articles by Nooter, K. Related Collections Neoplasia Oncogenes and Tumor Suppressors Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Brief report Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump Herman Burger, Hans van Tol, Antonius W. M. Boersma, Mariël Brok, Erik A. C. Wiemer, Gerrit Stoter, and Kees Nooter From the Department of Medical Oncology, Erasmus Medical Center Rotterdam, Daniel den Hoed Kliniek/Josephine Nefkens Institute, Rotterdam, The Netherlands. Imatinib mesylate (STI571), a potent tyrosine kinase inhibitor, is successfully used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors. However, the intended chronic oral administration of imatinib may lead to development of cellular resistance and subsequent treatment failure. Indeed, several molecular mechanisms leading to imatinib resistance have already been reported, including overexpression of the MDR1/ABCB1 drug pump. We examined whether imatinib is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump that is frequently overexpressed in human tumors. Using a panel of well-defined BCRP-overexpressing cell lines, we provide the first evidence that imatinib is a substrate for BCRP, that it competes with mitoxantrone for drug export, and that BCRP-mediated efflux can be reversed by the fumitremorgin C analog Ko-143. Since BCRP is highly expressed in the gastrointestinal tract, BCRP might not only play a role in cellular resistance of tumor cells but also influence the gastrointestinal absorption of imatinib. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Chapuy, M. Panse, U. Radunski, R. Koch, D. Wenzel, N. Inagaki, D. Haase, L. Truemper, and G. 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Verweij Improved Insight into Resistance Mechanisms to Imatinib in Gastrointestinal Stromal Tumors: A Basis for Novel Approaches and Individualization of Treatment Oncologist, June 1, 2007; 12(6): 719 - 726. [Abstract] [Full Text] [PDF] W. Liu, M. R. Baer, M. J. Bowman, P. Pera, X. Zheng, J. Morgan, R. A. Pandey, and A. R. Oseroff The Tyrosine Kinase Inhibitor Imatinib Mesylate Enhances the Efficacy of Photodynamic Therapy by Inhibiting ABCG2 Clin. Cancer Res., April 15, 2007; 13(8): 2463 - 2470. [Abstract] [Full Text] [PDF] G. Cusatis, V. Gregorc, J. Li, A. Spreafico, R. G. Ingersoll, J. Verweij, V. Ludovini, E. Villa, M. Hidalgo, A. Sparreboom, et al. Pharmacogenetics of ABCG2 and Adverse Reactions to Gefitinib J Natl Cancer Inst, December 6, 2006; 98(23): 1739 - 1742. [Abstract] [Full Text] [PDF] B. Sarkadi, L. Homolya, G. Szakacs, and A. Varadi Human Multidrug Resistance ABCB and ABCG Transporters: Participation in a Chemoimmunity Defense System. 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Mountford Functional ABCG2 is overexpressed on primary CML CD34+ cells and is inhibited by imatinib mesylate Blood, August 15, 2006; 108(4): 1370 - 1373. [Abstract] [Full Text] [PDF] T. Nakanishi, K. Shiozawa, B. A. Hassel, and D. D. Ross Complex interaction of BCRP/ABCG2 and imatinib in BCR-ABL-expressing cells: BCRP-mediated resistance to imatinib is attenuated by imatinib-induced reduction of BCRP expression Blood, July 15, 2006; 108(2): 678 - 684. [Abstract] [Full Text] [PDF] D. L. White, V. A. Saunders, P. Dang, J. Engler, A. C. W. Zannettino, A. C. Cambareri, S. R. Quinn, P. W. Manley, and T. P. Hughes OCT-1-mediated influx is a key determinant of the intracellular uptake of imatinib but not nilotinib (AMN107): reduced OCT-1 activity is the cause of low in vitro sensitivity to imatinib Blood, July 15, 2006; 108(2): 697 - 704. [Abstract] [Full Text] [PDF] M. Copland, A. Hamilton, L. J. Elrick, J. W. Baird, E. K. Allan, N. Jordanides, M. Barow, J. C. Mountford, and T. L. Holyoake Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction Blood, June 1, 2006; 107(11): 4532 - 4539. [Abstract] [Full Text] [PDF] G. Merino, A. I. Alvarez, M. M. Pulido, A. J. Molina, A. H. Schinkel, and J. G. Prieto BREAST CANCER RESISTANCE PROTEIN (BCRP/ABCG2) TRANSPORTS FLUOROQUINOLONE ANTIBIOTICS AND AFFECTS THEIR ORAL AVAILABILITY, PHARMACOKINETICS, AND MILK SECRETION Drug Metab. Dispos., April 1, 2006; 34(4): 690 - 695. [Abstract] [Full Text] [PDF] N. Theou, S. Gil, A. Devocelle, C. Julie, A. Lavergne-Slove, A. Beauchet, P. Callard, R. Farinotti, A. Le Cesne, A. Lemoine, et al. Multidrug Resistance Proteins in Gastrointestinal Stromal Tumors: Site-Dependent Expression and Initial Response to Imatinib Clin. Cancer Res., November 1, 2005; 11(21): 7593 - 7598. [Abstract] [Full Text] [PDF] L. C. Crossman, B. J. Druker, M. W. N. Deininger, M. Pirmohamed, L. Wang, and R. E. Clark hOCT 1 and resistance to imatinib Blood, August 1, 2005; 106(3): 1133 - 1134. [Full Text] [PDF] G. Merino, A. E. van Herwaarden, E. Wagenaar, J. W. Jonker, and A. H. Schinkel Sex-Dependent Expression and Activity of the ATP-Binding Cassette Transporter Breast Cancer Resistance Protein (BCRP/ABCG2) in Liver Mol. Pharmacol., May 1, 2005; 67(5): 1765 - 1771. [Abstract] [Full Text] [PDF] N. B. Elkind, Z. Szentpetery, A. Apati, C. Ozvegy-Laczka, G. Varady, O. Ujhelly, K. Szabo, L. Homolya, A. Varadi, L. Buday, et al. Multidrug Transporter ABCG2 Prevents Tumor Cell Death Induced by the Epidermal Growth Factor Receptor Inhibitor Iressa (ZD1839, Gefitinib) Cancer Res., March 1, 2005; 65(5): 1770 - 1777. [Abstract] [Full Text] [PDF] U. De Giorgi and J. Verweij Imatinib and gastrointestinal stromal tumors: Where do we go from here? Mol. Cancer Ther., March 1, 2005; 4(3): 495 - 501. [Abstract] [Full Text] [PDF] R. L. Ilaria Jr. Pathobiology of Lymphoid and Myeloid Blast Crisis and Management Issues Hematology, January 1, 2005; 2005(1): 188 - 194. [Abstract] [Full Text] [PDF]

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