Cancer Research Meeting Calendar EMT and Cancer Progression and Treatment
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by La Rosée, P.
Right arrow Articles by Druker, B. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by La Rosée, P.
Right arrow Articles by Druker, B. J.
[Cancer Research 62, 7149-7153, December 15, 2002]
© 2002 American Association for Cancer Research

Advances in Brief

Activity of the Bcr-Abl Kinase Inhibitor PD180970 against Clinically Relevant Bcr-Abl Isoforms That Cause Resistance to Imatinib Mesylate (Gleevec, STI571)1

Paul La Rosée, Amie S. Corbin, Eric P. Stoffregen, Michael W. Deininger and Brian J. Druker2

Oregon Health and Sciences University Cancer Institute, Division of Hematology and Medical Oncology, Portland, Oregon 97239 [P. L. R., A. S. C., E. P. S., M. W. D., B. J. D.], and III. Medizinische Universitätsklinik, Fakultät für klinische Medizin Mannheim der Universität Heidelberg, 68305 Mannheim, Germany [P. L. R.]

Imatinib mesylate, a selective inhibitor of the Abl tyrosine kinase, is effective as a single-agent therapy for chronic myelogenous leukemia. However, resistance has been reported, particularly in patients with advanced-stage disease. Mutations within the Abl kinase domain are a major cause of resistance, demonstrating that Bcr-Abl remains a critical drug target. Recently, a novel pyrido[2,3-d]pyrimidine derivative, PD180970, has been shown to potently inhibit Bcr-Abl and induce apoptosis in Bcr-Abl-expressing leukemic cells. We analyzed the inhibitory activity of PD180970 against Abl kinase domain mutations and cells expressing clinically relevant mutations. Our data indicate that PD180970 is active against several Bcr-Abl mutations that are resistant to imatinib and support the notion that developing additional Abl kinase inhibitors would be useful as a treatment strategy for chronic myelogenous leukemia.




This article has been cited by other articles:


Home page
 BloodHome page
B. J. Druker
Translation of the Philadelphia chromosome into therapy for CML
Blood, December 15, 2008; 112(13): 4808 - 4817.
[Abstract] [Full Text] [PDF]

Home page
 Schizophr BullHome page
M. J. Arranz and S. Kapur
Pharmacogenetics in Psychiatry: Are We Ready for Widespread Clinical Use?
Schizophr Bull, November 1, 2008; 34(6): 1130 - 1144.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
M. Zhang, W. Fu, S. Prabhu, J. C. Moore, J. Ko, J. W. Kim, B. J. Druker, V. Trapp, J. Fruehauf, H. Gram, et al.
Inhibition of Polysome Assembly Enhances Imatinib Activity against Chronic Myelogenous Leukemia and Overcomes Imatinib Resistance
Mol. Cell. Biol., October 15, 2008; 28(20): 6496 - 6509.
[Abstract] [Full Text] [PDF]

Home page
 aacredbookHome page
A. Fernandez, A. Sanguino, Z. Peng, A. Crespo, E. Ozturk, X. Zhang, S. Wang, W. Bornmann, and G. Lopez-Berestein
Rational Drug Redesign to Overcome Drug Resistance in Cancer Therapy: Imatinib Moving Target
Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 589 - 599.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
P. Ramirez and J. F. DiPersio
Therapy Options in Imatinib Failures
Oncologist, April 1, 2008; 13(4): 424 - 434.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. Mayerhofer, K. V. Gleixner, J. Mayerhofer, G. Hoermann, E. Jaeger, K. J. Aichberger, R. G. Ott, K. Greish, H. Nakamura, S. Derdak, et al.
Targeting of heat shock protein 32 (Hsp32)/heme oxygenase-1 (HO-1) in leukemic cells in chronic myeloid leukemia: a novel approach to overcome resistance against imatinib
Blood, February 15, 2008; 111(4): 2200 - 2210.
[Abstract] [Full Text] [PDF]

Home page
 haematolHome page
T. Ernst, P. Erben, M. C. Muller, P. Paschka, T. Schenk, J. Hoffmann, S. Kreil, P. La Rosee, R. Hehlmann, and A. Hochhaus
Dynamics of BCR-ABL mutated clones prior to hematologic or cytogenetic resistance to imatinib
Haematologica, February 1, 2008; 93(2): 186 - 192.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
M. Rahmani, T. K. Nguyen, P. Dent, and S. Grant
The Multikinase Inhibitor Sorafenib Induces Apoptosis in Highly Imatinib Mesylate-Resistant Bcr/Abl+ Human Leukemia Cells in Association with Signal Transducer and Activator of Transcription 5 Inhibition and Myeloid Cell Leukemia-1 Down-Regulation
Mol. Pharmacol., September 1, 2007; 72(3): 788 - 795.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. Dasmahapatra, N. Yerram, Y. Dai, P. Dent, and S. Grant
Synergistic Interactions between Vorinostat and Sorafenib in Chronic Myelogenous Leukemia Cells Involve Mcl-1 and p21CIP1 Down-Regulation
Clin. Cancer Res., July 15, 2007; 13(14): 4280 - 4290.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
A. Fernandez, A. Sanguino, Z. Peng, A. Crespo, E. Ozturk, X. Zhang, S. Wang, W. Bornmann, and G. Lopez-Berestein
Rational Drug Redesign to Overcome Drug Resistance in Cancer Therapy: Imatinib Moving Target
Cancer Res., May 1, 2007; 67(9): 4028 - 4033.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
T. K. Nguyen, M. Rahmani, H. Harada, P. Dent, and S. Grant
MEK1/2 inhibitors sensitize Bcr/Abl+ human leukemia cells to the dual Abl/Src inhibitor BMS-354/825
Blood, May 1, 2007; 109(9): 4006 - 4015.
[Abstract] [Full Text] [PDF]

Home page
 ANN INTERN MEDHome page
H. M. Kantarjian, M. Talpaz, F. Giles, S. O'Brien, and J. Cortes
New Insights into the Pathophysiology of Chronic Myeloid Leukemia and Imatinib Resistance
Ann Intern Med, December 19, 2006; 145(12): 913 - 923.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
P. La Rosee, T. Jia, S. Demehri, N. Hartel, P. de Vries, L. Bonham, D. Hollenback, J. W. Singer, J. V. Melo, B. J. Druker, et al.
Antileukemic Activity of Lysophosphatidic Acid Acyltransferase-{beta} Inhibitor CT32228 in Chronic Myelogenous Leukemia Sensitive and Resistant to Imatinib.
Clin. Cancer Res., November 1, 2006; 12(21): 6540 - 6546.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
W. Fiskus, M. Pranpat, M. Balasis, P. Bali, V. Estrella, S. Kumaraswamy, R. Rao, K. Rocha, B. Herger, F. Lee, et al.
Cotreatment with Vorinostat (Suberoylanilide Hydroxamic Acid) Enhances Activity of Dasatinib (BMS-354825) against Imatinib Mesylate-Sensitive or Imatinib Mesylate-Resistant Chronic Myelogenous Leukemia Cells.
Clin. Cancer Res., October 1, 2006; 12(19): 5869 - 5878.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
N. von Bubnoff, P. W. Manley, J. Mestan, J. Sanger, C. Peschel, and J. Duyster
Bcr-Abl resistance screening predicts a limited spectrum of point mutations to be associated with clinical resistance to the Abl kinase inhibitor nilotinib (AMN107)
Blood, August 15, 2006; 108(4): 1328 - 1333.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
W. Fiskus, M. Pranpat, P. Bali, M. Balasis, S. Kumaraswamy, S. Boyapalle, K. Rocha, J. Wu, F. Giles, P. W. Manley, et al.
Combined effects of novel tyrosine kinase inhibitor AMN107 and histone deacetylase inhibitor LBH589 against Bcr-Abl-expressing human leukemia cells
Blood, July 15, 2006; 108(2): 645 - 652.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
B. J. Druker
Circumventing resistance to kinase-inhibitor therapy.
N. Engl. J. Med., June 15, 2006; 354(24): 2594 - 2596.
[Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T. K. Nguyen, M. Rahmani, N. Gao, L. Kramer, A. S. Corbin, B. J. Druker, P. Dent, and S. Grant
Synergistic interactions between DMAG and mitogen-activated protein kinase kinase 1/2 inhibitors in Bcr/abl+ leukemia cells sensitive and resistant to imatinib mesylate.
Clin. Cancer Res., April 1, 2006; 12(7 Pt 1): 2239 - 2247.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T. O'Hare, D. K. Walters, E. P. Stoffregen, D. W. Sherbenou, M. C. Heinrich, M. W.N. Deininger, and B. J. Druker
Combined Abl Inhibitor Therapy for Minimizing Drug Resistance in Chronic Myeloid Leukemia: Src/Abl Inhibitors Are Compatible with Imatinib
Clin. Cancer Res., October 1, 2005; 11(19): 6987 - 6993.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. A. Carter, L. M. Wodicka, N. P. Shah, A. M. Velasco, M. A. Fabian, D. K. Treiber, Z. V. Milanov, C. E. Atteridge, W. H. Biggs III, P. T. Edeen, et al.
Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases
PNAS, August 2, 2005; 102(31): 11011 - 11016.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. S. Corbin, S. Demehri, I. J. Griswold, Y. Wang, C. A. Metcalf III, R. Sundaramoorthi, W. C. Shakespeare, J. Snodgrass, S. Wardwell, D. Dalgarno, et al.
In vitro and in vivo activity of ATP-based kinase inhibitors AP23464 and AP23848 against activation-loop mutants of Kit
Blood, July 1, 2005; 106(1): 227 - 234.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
T. O'Hare, D. K. Walters, E. P. Stoffregen, T. Jia, P. W. Manley, J. Mestan, S. W. Cowan-Jacob, F. Y. Lee, M. C. Heinrich, M. W.N. Deininger, et al.
In vitro Activity of Bcr-Abl Inhibitors AMN107 and BMS-354825 against Clinically Relevant Imatinib-Resistant Abl Kinase Domain Mutants
Cancer Res., June 1, 2005; 65(11): 4500 - 4505.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
N. C. Wolff, D. R. Veach, W. P. Tong, W. G. Bornmann, B. Clarkson, and R. L. Ilaria Jr
PD166326, a novel tyrosine kinase inhibitor, has greater antileukemic activity than imatinib mesylate in a murine model of chronic myeloid leukemia
Blood, May 15, 2005; 105(10): 3995 - 4003.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
P.-H. Tseng, H.-P. Lin, J. Zhu, K.-F. Chen, E. M. Hade, D. C. Young, J. C. Byrd, M. Grever, K. Johnson, B. J. Druker, et al.
Synergistic interactions between imatinib mesylate and the novel phosphoinositide-dependent kinase-1 inhibitor OSU-03012 in overcoming imatinib mesylate resistance
Blood, May 15, 2005; 105(10): 4021 - 4027.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
Y. P. Lim
Mining the Tumor Phosphoproteome for Cancer Markers
Clin. Cancer Res., May 1, 2005; 11(9): 3163 - 3169.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. Deininger, E. Buchdunger, and B. J. Druker
The development of imatinib as a therapeutic agent for chronic myeloid leukemia
Blood, April 1, 2005; 105(7): 2640 - 2653.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
N. von Bubnoff, D. R. Veach, H. van der Kuip, W. E. Aulitzky, J. Sanger, P. Seipel, W. G. Bornmann, C. Peschel, B. Clarkson, and J. Duyster
A cell-based screen for resistance of Bcr-Abl-positive leukemia identifies the mutation pattern for PD166326, an alternative Abl kinase inhibitor
Blood, February 15, 2005; 105(4): 1652 - 1659.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
P. George, P. Bali, S. Annavarapu, A. Scuto, W. Fiskus, F. Guo, C. Sigua, G. Sondarva, L. Moscinski, P. Atadja, et al.
Combination of the histone deacetylase inhibitor LBH589 and the hsp90 inhibitor 17-AAG is highly active against human CML-BC cells and AML cells with activating mutation of FLT-3
Blood, February 15, 2005; 105(4): 1768 - 1776.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
K. Gumireddy, S. J. Baker, S. C. Cosenza, P. John, A. D. Kang, K. A. Robell, M. V. R. Reddy, and E. P. Reddy
A non-ATP-competitive inhibitor of BCR-ABL overrides imatinib resistance
PNAS, February 8, 2005; 102(6): 1992 - 1997.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. ProteomicsHome page
J. Wissing, K. Godl, D. Brehmer, S. Blencke, M. Weber, P. Habenberger, M. Stein-Gerlach, A. Missio, M. Cotten, S. Muller, et al.
Chemical Proteomic Analysis Reveals Alternative Modes of Action for Pyrido[2,3-d]pyrimidine Kinase Inhibitors
Mol. Cell. Proteomics, December 1, 2004; 3(12): 1181 - 1193.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. S. Corbin, I. J. Griswold, P. La Rosee, K. W. H. Yee, M. C. Heinrich, C. L. Reimer, B. J. Druker, and M. W. N. Deininger
Sensitivity of oncogenic KIT mutants to the kinase inhibitors MLN518 and PD180970
Blood, December 1, 2004; 104(12): 3754 - 3757.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
T. O'Hare, R. Pollock, E. P. Stoffregen, J. A. Keats, O. M. Abdullah, E. M. Moseson, V. M. Rivera, H. Tang, C. A. Metcalf III, R. S. Bohacek, et al.
Inhibition of wild-type and mutant Bcr-Abl by AP23464, a potent ATP-based oncogenic protein kinase inhibitor: implications for CML
Blood, October 15, 2004; 104(8): 2532 - 2539.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Dai, M. Rahmani, S. J. Corey, P. Dent, and S. Grant
A Bcr/Abl-independent, Lyn-dependent Form of Imatinib Mesylate (STI-571) Resistance Is Associated with Altered Expression of Bcl-2
J. Biol. Chem., August 13, 2004; 279(33): 34227 - 34239.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
N. P. Shah, C. Tran, F. Y. Lee, P. Chen, D. Norris, and C. L. Sawyers
Overriding Imatinib Resistance with a Novel ABL Kinase Inhibitor
Science, July 16, 2004; 305(5682): 399 - 401.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
Y. Dai, M. Rahmani, X.-Y. Pei, P. Dent, and S. Grant
Bortezomib and flavopiridol interact synergistically to induce apoptosis in chronic myeloid leukemia cells resistant to imatinib mesylate through both Bcr/Abl-dependent and -independent mechanisms
Blood, July 15, 2004; 104(2): 509 - 518.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
P. La Rosee, K. Johnson, A. S. Corbin, E. P. Stoffregen, E. M. Moseson, S. Willis, M. M. Mauro, J. V. Melo, M. W. Deininger, and B. J. Druker
In vitro efficacy of combined treatment depends on the underlying mechanism of resistance in imatinib-resistant Bcr-Abl-positive cell lines
Blood, January 1, 2004; 103(1): 208 - 215.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
B. J. Druker
Imatinib As a Paradigm of Targeted Therapies
J. Clin. Oncol., December 1, 2003; 21(90230): 239s - 245.
[Full Text] [PDF]

Home page
 BloodHome page
C. Yu, M. Rahmani, D. Conrad, M. Subler, P. Dent, and S. Grant
The proteasome inhibitor bortezomib interacts synergistically with histone deacetylase inhibitors to induce apoptosis in Bcr/Abl+ cells sensitive and resistant to STI571
Blood, November 15, 2003; 102(10): 3765 - 3774.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
N. von Bubnoff, D. R. Veach, W. T. Miller, W. Li, J. Sanger, C. Peschel, W. G. Bornmann, B. Clarkson, and J. Duyster
Inhibition of Wild-Type and Mutant Bcr-Abl by Pyrido-Pyrimidine-Type Small Molecule Kinase Inhibitors
Cancer Res., October 1, 2003; 63(19): 6395 - 6404.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
M. W. N. Deininger and B. J. Druker
Specific Targeted Therapy of Chronic Myelogenous Leukemia with Imatinib
Pharmacol. Rev., September 1, 2003; 55(3): 401 - 423.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. Nimmanapalli, L. Fuino, P. Bali, M. Gasparetto, M. Glozak, J. Tao, L. Moscinski, C. Smith, J. Wu, R. Jove, et al.
Histone Deacetylase Inhibitor LAQ824 Both Lowers Expression and Promotes Proteasomal Degradation of Bcr-Abl and Induces Apoptosis of Imatinib Mesylate-sensitive or -refractory Chronic Myelogenous Leukemia-Blast Crisis Cells
Cancer Res., August 15, 2003; 63(16): 5126 - 5135.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. S. Corbin, P. L. Rosee, E. P. Stoffregen, B. J. Druker, and M. W. Deininger
Several Bcr-Abl kinase domain mutants associated with imatinib mesylate resistance remain sensitive to imatinib
Blood, June 1, 2003; 101(11): 4611 - 4614.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. Yu, M. Rahmani, J. Almenara, M. Subler, G. Krystal, D. Conrad, L. Varticovski, P. Dent, and S. Grant
Histone Deacetylase Inhibitors Promote STI571-mediated Apoptosis in STI571-sensitive and -resistant Bcr/Abl+ Human Myeloid Leukemia Cells
Cancer Res., May 1, 2003; 63(9): 2118 - 2126.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2002 by the American Association for Cancer Research.