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Molecular Cancer Therapeutics
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Preclinical Development

Active Efflux of Dasatinib from the Brain Limits Efficacy against Murine Glioblastoma: Broad Implications for the Clinical Use of Molecularly Targeted Agents

Sagar Agarwal, Rajendar K. Mittapalli, David M. Zellmer, Jose L. Gallardo, Randy Donelson, Charlie Seiler, Stacy A. Decker, Karen S. SantaCruz, Jenny L. Pokorny, Jann N. Sarkaria, William F. Elmquist and John R. Ohlfest
Sagar Agarwal
Departments of 1Pharmaceutics, 2Pediatrics, 3Neuroscience, 4Laboratory Medicine and Pathology, and 5Neurosurgery; 6Brain Barriers Research Center, University of Minnesota, Minneapolis; and 7Department of Radiation Oncology, Mayo Clinic, Rochester, Minneapolis
Departments of 1Pharmaceutics, 2Pediatrics, 3Neuroscience, 4Laboratory Medicine and Pathology, and 5Neurosurgery; 6Brain Barriers Research Center, University of Minnesota, Minneapolis; and 7Department of Radiation Oncology, Mayo Clinic, Rochester, Minneapolis
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Rajendar K. Mittapalli
Departments of 1Pharmaceutics, 2Pediatrics, 3Neuroscience, 4Laboratory Medicine and Pathology, and 5Neurosurgery; 6Brain Barriers Research Center, University of Minnesota, Minneapolis; and 7Department of Radiation Oncology, Mayo Clinic, Rochester, Minneapolis
Departments of 1Pharmaceutics, 2Pediatrics, 3Neuroscience, 4Laboratory Medicine and Pathology, and 5Neurosurgery; 6Brain Barriers Research Center, University of Minnesota, Minneapolis; and 7Department of Radiation Oncology, Mayo Clinic, Rochester, Minneapolis
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David M. Zellmer
Departments of 1Pharmaceutics, 2Pediatrics, 3Neuroscience, 4Laboratory Medicine and Pathology, and 5Neurosurgery; 6Brain Barriers Research Center, University of Minnesota, Minneapolis; and 7Department of Radiation Oncology, Mayo Clinic, Rochester, Minneapolis
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Jose L. Gallardo
Departments of 1Pharmaceutics, 2Pediatrics, 3Neuroscience, 4Laboratory Medicine and Pathology, and 5Neurosurgery; 6Brain Barriers Research Center, University of Minnesota, Minneapolis; and 7Department of Radiation Oncology, Mayo Clinic, Rochester, Minneapolis
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Randy Donelson
Departments of 1Pharmaceutics, 2Pediatrics, 3Neuroscience, 4Laboratory Medicine and Pathology, and 5Neurosurgery; 6Brain Barriers Research Center, University of Minnesota, Minneapolis; and 7Department of Radiation Oncology, Mayo Clinic, Rochester, Minneapolis
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Charlie Seiler
Departments of 1Pharmaceutics, 2Pediatrics, 3Neuroscience, 4Laboratory Medicine and Pathology, and 5Neurosurgery; 6Brain Barriers Research Center, University of Minnesota, Minneapolis; and 7Department of Radiation Oncology, Mayo Clinic, Rochester, Minneapolis
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Stacy A. Decker
Departments of 1Pharmaceutics, 2Pediatrics, 3Neuroscience, 4Laboratory Medicine and Pathology, and 5Neurosurgery; 6Brain Barriers Research Center, University of Minnesota, Minneapolis; and 7Department of Radiation Oncology, Mayo Clinic, Rochester, Minneapolis
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Karen S. SantaCruz
Departments of 1Pharmaceutics, 2Pediatrics, 3Neuroscience, 4Laboratory Medicine and Pathology, and 5Neurosurgery; 6Brain Barriers Research Center, University of Minnesota, Minneapolis; and 7Department of Radiation Oncology, Mayo Clinic, Rochester, Minneapolis
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Jenny L. Pokorny
Departments of 1Pharmaceutics, 2Pediatrics, 3Neuroscience, 4Laboratory Medicine and Pathology, and 5Neurosurgery; 6Brain Barriers Research Center, University of Minnesota, Minneapolis; and 7Department of Radiation Oncology, Mayo Clinic, Rochester, Minneapolis
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Jann N. Sarkaria
Departments of 1Pharmaceutics, 2Pediatrics, 3Neuroscience, 4Laboratory Medicine and Pathology, and 5Neurosurgery; 6Brain Barriers Research Center, University of Minnesota, Minneapolis; and 7Department of Radiation Oncology, Mayo Clinic, Rochester, Minneapolis
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William F. Elmquist
Departments of 1Pharmaceutics, 2Pediatrics, 3Neuroscience, 4Laboratory Medicine and Pathology, and 5Neurosurgery; 6Brain Barriers Research Center, University of Minnesota, Minneapolis; and 7Department of Radiation Oncology, Mayo Clinic, Rochester, Minneapolis
Departments of 1Pharmaceutics, 2Pediatrics, 3Neuroscience, 4Laboratory Medicine and Pathology, and 5Neurosurgery; 6Brain Barriers Research Center, University of Minnesota, Minneapolis; and 7Department of Radiation Oncology, Mayo Clinic, Rochester, Minneapolis
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John R. Ohlfest
Departments of 1Pharmaceutics, 2Pediatrics, 3Neuroscience, 4Laboratory Medicine and Pathology, and 5Neurosurgery; 6Brain Barriers Research Center, University of Minnesota, Minneapolis; and 7Department of Radiation Oncology, Mayo Clinic, Rochester, Minneapolis
Departments of 1Pharmaceutics, 2Pediatrics, 3Neuroscience, 4Laboratory Medicine and Pathology, and 5Neurosurgery; 6Brain Barriers Research Center, University of Minnesota, Minneapolis; and 7Department of Radiation Oncology, Mayo Clinic, Rochester, Minneapolis
Departments of 1Pharmaceutics, 2Pediatrics, 3Neuroscience, 4Laboratory Medicine and Pathology, and 5Neurosurgery; 6Brain Barriers Research Center, University of Minnesota, Minneapolis; and 7Department of Radiation Oncology, Mayo Clinic, Rochester, Minneapolis
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DOI: 10.1158/1535-7163.MCT-12-0552 Published October 2012
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Article Information

Volume 11, Issue 10, pp. 2183-2192

DOI 
https://doi.org/10.1158/1535-7163.MCT-12-0552
PubMed 
22891038

Published By 
American Association for Cancer Research
Print ISSN 
1535-7163
Online ISSN 
1538-8514
History 
  • Received May 31, 2012
  • Revision received July 20, 2012
  • Accepted August 6, 2012
  • Published first August 13, 2012.

Article Versions

  • Previous version (August 13, 2012 - 13:36).
  • Previous version (October 2, 2012 - 14:34).
  • You are viewing the most recent version of this article.
Copyright & Usage 
©2012 American Association for Cancer Research.

Author Information

  1. Sagar Agarwal1,6,
  2. Rajendar K. Mittapalli1,6,
  3. David M. Zellmer2,
  4. Jose L. Gallardo2,
  5. Randy Donelson2,
  6. Charlie Seiler2,
  7. Stacy A. Decker3,
  8. Karen S. SantaCruz4,
  9. Jenny L. Pokorny7,
  10. Jann N. Sarkaria7,
  11. William F. Elmquist1,6, and
  12. John R. Ohlfest2,5,6
  1. Authors' Affiliations: Departments of 1Pharmaceutics, 2Pediatrics, 3Neuroscience, 4Laboratory Medicine and Pathology, and 5Neurosurgery; 6Brain Barriers Research Center, University of Minnesota, Minneapolis; and 7Department of Radiation Oncology, Mayo Clinic, Rochester, Minneapolis
  1. Corresponding Author:
    John Ohlfest, Department of Pediatrics, University of Minnesota, 420 Delaware St. SE, MMC 366, Minneapolis, MN 55455. Phone: 612-626-2491; Fax: 612-626-2490; E-mail: ohlfe001{at}umn.edu
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Molecular Cancer Therapeutics: 11 (10)
October 2012
Volume 11, Issue 10
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Active Efflux of Dasatinib from the Brain Limits Efficacy against Murine Glioblastoma: Broad Implications for the Clinical Use of Molecularly Targeted Agents
Sagar Agarwal, Rajendar K. Mittapalli, David M. Zellmer, Jose L. Gallardo, Randy Donelson, Charlie Seiler, Stacy A. Decker, Karen S. SantaCruz, Jenny L. Pokorny, Jann N. Sarkaria, William F. Elmquist and John R. Ohlfest
Mol Cancer Ther October 1 2012 (11) (10) 2183-2192; DOI: 10.1158/1535-7163.MCT-12-0552

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Active Efflux of Dasatinib from the Brain Limits Efficacy against Murine Glioblastoma: Broad Implications for the Clinical Use of Molecularly Targeted Agents
Sagar Agarwal, Rajendar K. Mittapalli, David M. Zellmer, Jose L. Gallardo, Randy Donelson, Charlie Seiler, Stacy A. Decker, Karen S. SantaCruz, Jenny L. Pokorny, Jann N. Sarkaria, William F. Elmquist and John R. Ohlfest
Mol Cancer Ther October 1 2012 (11) (10) 2183-2192; DOI: 10.1158/1535-7163.MCT-12-0552
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