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Science 305 (5682): 399-401

Copyright © 2004 by the American Association for the Advancement of Science

Overriding Imatinib Resistance with a Novel ABL Kinase Inhibitor

Neil P. Shah,1 Chris Tran,1,2 Francis Y. Lee,3 Ping Chen,3 Derek Norris,3 Charles L. Sawyers1,2*

Abstract: Resistance to the ABL kinase inhibitor imatinib (STI571 or Gleevec) in chronic myeloid leukemia (CML) occurs through selection for tumor cells harboring BCR-ABL kinase domain point mutations that interfere with drug binding. Crystallographic studies predict that most imatinib-resistant mutants should remain sensitive to inhibitors that bind ABL with less stringent conformational requirements. BMS-354825 is an orally bioavailable ABL kinase inhibitor with two-log increased potency relative to imatinib that retains activity against 14 of 15 imatinib-resistant BCR-ABL mutants. BMS-354825 prolongs survival of mice with BCR-ABL–driven disease and inhibits proliferation of BCR-ABL–positive bone marrow progenitor cells from patients with imatinib-sensitive and imatinib-resistant CML. These data illustrate how molecular insight into kinase inhibitor resistance can guide the design of second-generation targeted therapies.

1 Division of Hematology and Oncology, Department of Medicine, The David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
2 Howard Hughes Medical Institute, The David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA.
3 Bristol-Myers Squibb Oncology, Princeton, NJ, USA.

* To whom correspondence should be addressed. E-mail: csawyers{at}

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A. Agarwal, R. J. MacKenzie, R. Pippa, C. A. Eide, J. Oddo, J. W. Tyner, R. Sears, M. P. Vitek, M. D. Odero, D. J. Christensen, et al. (2014)
Clin. Cancer Res. 20, 2092-2103
   Abstract »    Full Text »    PDF »
Quantitative Assessment of Mutant Allele Burden in Solid Tumors by Semiconductor-Based Next-Generation Sequencing.
B. P. Portier, R. Kanagal-Shamanna, R. Luthra, R. Singh, M. J. Routbort, B. Handal, N. Reddy, B. A. Barkoh, Z. Zuo, L. J. Medeiros, et al. (2014)
Am J Clin Pathol 141, 559-572
   Abstract »    Full Text »    PDF »
Kinase-Independent Mechanisms of Resistance of Leukemia Stem Cells to Tyrosine Kinase Inhibitors.
C. V. Ichim (2014)
Stem Cells Trans Med 3, 405-415
   Abstract »    Full Text »    PDF »
Molecular dynamics reveal BCR-ABL1 polymutants as a unique mechanism of resistance to PAN-BCR-ABL1 kinase inhibitor therapy.
D. L. Gibbons, S. Pricl, P. Posocco, E. Laurini, M. Fermeglia, H. Sun, M. Talpaz, N. Donato, and A. Quintas-Cardama (2014)
PNAS 111, 3550-3555
   Abstract »    Full Text »    PDF »
BCR-ABL residues interacting with ponatinib are critical to preserve the tumorigenic potential of the oncoprotein.
P. Buffa, C. Romano, A. Pandini, M. Massimino, E. Tirro, F. Di Raimondo, L. Manzella, F. Fraternali, and P. G. Vigneri (2014)
FASEB J 28, 1221-1236
   Abstract »    Full Text »    PDF »
NMR reveals the allosteric opening and closing of Abelson tyrosine kinase by ATP-site and myristoyl pocket inhibitors.
L. Skora, J. Mestan, D. Fabbro, W. Jahnke, and S. Grzesiek (2013)
PNAS 110, E4437-E4445
   Abstract »    Full Text »    PDF »
Cross talk between Wnt/{beta}-catenin and Irf8 in leukemia progression and drug resistance.
M. Scheller, J. Schonheit, K. Zimmermann, U. Leser, F. Rosenbauer, and A. Leutz (2013)
J. Exp. Med. 210, 2239-2256
   Abstract »    Full Text »    PDF »
From Bench to Bedside: Lessons Learned in Translating Preclinical Studies in Cancer Drug Development.
C. H. Lieu, A.-C. Tan, S. Leong, J. R. Diamond, and S. G. Eckhardt (2013)
J Natl Cancer Inst 105, 1441-1456
   Abstract »    Full Text »    PDF »
Threshold Levels of ABL Tyrosine Kinase Inhibitors Retained in Chronic Myeloid Leukemia Cells Determine Their Commitment to Apoptosis.
T. O'Hare, C. A. Eide, A. Agarwal, L. T. Adrian, M. S. Zabriskie, R. J. MacKenzie, D. H. LaTocha, K. J. Johnson, H. You, J. Luo, et al. (2013)
Cancer Res. 73, 3356-3370
   Abstract »    Full Text »    PDF »
Ipilimumab, Vemurafenib, Dabrafenib, and Trametinib: Synergistic Competitors in the Clinical Management of BRAF Mutant Malignant Melanoma.
J. J. Luke and F. S. Hodi (2013)
Oncologist 18, 717-725
   Abstract »    Full Text »    PDF »
SRC Signaling Is Crucial in the Growth of Synovial Sarcoma Cells.
S. Michels, M. Trautmann, E. Sievers, D. Kindler, S. Huss, M. Renner, N. Friedrichs, J. Kirfel, S. Steiner, E. Endl, et al. (2013)
Cancer Res. 73, 2518-2528
   Abstract »    Full Text »    PDF »
Chemotherapy-related cardiotoxicity.
S. Aggarwal, J. Kamboj, and R. Arora (2013)
Therapeutic Advances in Cardiovascular Disease 7, 87-98
   Abstract »    PDF »
A novel small molecule RAD51 inactivator overcomes imatinib-resistance in chronic myeloid leukaemia.
J. Zhu, L. Zhou, G. Wu, H. Konig, X. Lin, G. Li, X.-L. Qiu, C.-F. Chen, C.-M. Hu, E. Goldblatt, et al. (2013)
EMBO Mol Med. 5, 353-365
   Abstract »    Full Text »    PDF »
Overcoming mutation-based resistance to antiandrogens with rational drug design.
M. D. Balbas, M. J. Evans, D. J. Hosfield, J. Wongvipat, V. K. Arora, P. A. Watson, Y. Chen, G. L. Greene, Y. Shen, and C. L. Sawyers (2013)
eLife Sci 2, e00499
   Abstract »    Full Text »    PDF »
Myeloproliferative neoplasms.
R. L. Levine and R. V. Tiu (2013)
American Society of Hematology Self-Assessment Program 2013, 401-450
   Full Text »    PDF »
Cell biology: A key driver of therapeutic innovation.
O. Hantschel and G. Superti-Furga (2012)
J. Cell Biol. 199, 571-575
   Abstract »    Full Text »    PDF »
Stem Cell Factor Receptor/c-Kit: From Basic Science to Clinical Implications.
J. Lennartsson and L. Ronnstrand (2012)
Physiol Rev 92, 1619-1649
   Abstract »    Full Text »    PDF »
The Growing Arsenal of ATP-Competitive and Allosteric Inhibitors of BCR-ABL.
O. Hantschel, F. Grebien, and G. Superti-Furga (2012)
Cancer Res. 72, 4890-4895
   Abstract »    Full Text »    PDF »
10 Years of Progress in Chronic Myelogenous Leukemia.
E. Jabbour, M. S. Mathisen, and S. O'Brien (2012)
J Natl Compr Canc Netw 10, 1049-1053
   Full Text »    PDF »
Acute Lymphoblastic Leukemia.
J. C. Alvarnas, P. A. Brown, P. Aoun, K. K. Ballen, N. Bellam, W. Blum, M. W. Boyer, H. E. Carraway, P. F. Coccia, S. E. Coutre, et al. (2012)
J Natl Compr Canc Netw 10, 858-914
   Abstract »    Full Text »    PDF »
Role of Src Tyrosine Kinases in Experimental Pulmonary Hypertension.
S. S. Pullamsetti, E. M. Berghausen, S. Dabral, A. Tretyn, E. Butrous, R. Savai, G. Butrous, B. K. Dahal, R. P. Brandes, H. A. Ghofrani, et al. (2012)
Arterioscler Thromb Vasc Biol 32, 1354-1365
   Abstract »    Full Text »    PDF »
Dasatinib inhibits proinflammatory functions of mature human neutrophils.
K. Futosi, T. Nemeth, R. Pick, T. Vantus, B. Walzog, and A. Mocsai (2012)
Blood 119, 4981-4991
   Abstract »    Full Text »    PDF »
Structure, Regulation, Signaling, and Targeting of Abl Kinases in Cancer.
O. Hantschel (2012)
Genes & Cancer 3, 436-446
   Abstract »    Full Text »    PDF »
The Ins and Outs of Bcr-Abl Inhibition.
E. P. Reddy and A. K. Aggarwal (2012)
Genes & Cancer 3, 447-454
   Abstract »    Full Text »    PDF »
Impact of Genomics on Personalized Cancer Medicine.
C. L. Arteaga and J. Baselga (2012)
Clin. Cancer Res. 18, 612-618
   Abstract »    Full Text »    PDF »
Overcoming CML acquired resistance by specific inhibition of Aurora A kinase in the KCL-22 cell model.
H. Yuan, Z. Wang, H. Zhang, M. Roth, R. Bhatia, and W. Y. Chen (2012)
Carcinogenesis 33, 285-293
   Abstract »    Full Text »    PDF »
Chronic Myelogenous Leukemia.
S. O'Brien, C. N. Abboud, M. Akhtari, J. Altman, E. Berman, D. J. DeAngelo, S. Devine, A. T. Fathi, J. Gotlib, M. Jagasia, et al. (2012)
J Natl Compr Canc Netw 10, 64-110
   Full Text »    PDF »
Characterization of kinase inhibitors using different phosphorylation states of colony stimulating factor-1 receptor tyrosine kinase.
D. Kitagawa, M. Gouda, Y. Kirii, N. Sugiyama, Y. Ishihama, I. Fujii, Y. Narumi, K. Akita, and K. Yokota (2012)
J. Biochem. 151, 47-55
   Abstract »    Full Text »    PDF »
Tyrosine Kinase Inhibitor Therapy for Chronic Myeloid Leukemia: Approach to Patients with Treatment-Naive or Refractory Chronic-Phase Disease.
C. C. Smith and N. P. Shah (2011)
Hematology 2011, 121-127
   Abstract »    Full Text »    PDF »
A phase I study of dasatinib and weekly paclitaxel for metastatic breast cancer.
M. N. Fornier, P. G. Morris, A. Abbruzzi, G. D'Andrea, T. Gilewski, J. Bromberg, C. Dang, M. Dickler, S. Modi, A. D. Seidman, et al. (2011)
Ann. Onc. 22, 2575-2581
   Abstract »    Full Text »    PDF »
Novel Therapies for Metastatic Castrate-Resistant Prostate Cancer.
F. Dayyani, G. E. Gallick, C. J. Logothetis, and P. G. Corn (2011)
J Natl Cancer Inst 103, 1665-1675
   Abstract »    Full Text »    PDF »
The BCR-ABL35INS insertion/truncation mutant is kinase-inactive and does not contribute to tyrosine kinase inhibitor resistance in chronic myeloid leukemia.
T. O'Hare, M. S. Zabriskie, C. A. Eide, A. Agarwal, L. T. Adrian, H. You, A. S. Corbin, F. Yang, R. D. Press, V. M. Rivera, et al. (2011)
Blood 118, 5250-5254
   Abstract »    Full Text »    PDF »
Leukemic stem cell persistence in chronic myeloid leukemia patients with sustained undetectable molecular residual disease.
J.-C. Chomel, M.-L. Bonnet, N. Sorel, A. Bertrand, M.-C. Meunier, S. Fichelson, M. Melkus, A. Bennaceur-Griscelli, F. Guilhot, and A. G. Turhan (2011)
Blood 118, 3657-3660
   Abstract »    Full Text »    PDF »
The Role of p27Kip1 in Dasatinib-Enhanced Paclitaxel Cytotoxicity in Human Ovarian Cancer Cells.
X.-F. Le, W. Mao, G. He, F.-X. Claret, W. Xia, A. A. Ahmed, M.-C. Hung, Z. H. Siddik, and R. C. Bast Jr (2011)
J Natl Cancer Inst 103, 1403-1422
   Abstract »    Full Text »    PDF »
BCR-ABL kinase domain mutation analysis in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: recommendations from an expert panel on behalf of European LeukemiaNet.
S. Soverini, A. Hochhaus, F. E. Nicolini, F. Gruber, T. Lange, G. Saglio, F. Pane, M. C. Muller, T. Ernst, G. Rosti, et al. (2011)
Blood 118, 1208-1215
   Abstract »    Full Text »    PDF »
Dissecting Therapeutic Resistance to RAF Inhibition in Melanoma by Tumor Genomic Profiling.
N. Wagle, C. Emery, M. F. Berger, M. J. Davis, A. Sawyer, P. Pochanard, S. M. Kehoe, C. M. Johannessen, L. E. MacConaill, W. C. Hahn, et al. (2011)
J. Clin. Oncol. 29, 3085-3096
   Abstract »    Full Text »    PDF »
Profile of Charles L. Sawyers.
P. Nair (2011)
PNAS 108, 10033-10035
   Full Text »    PDF »
Outcome of patients with chronic myeloid leukemia with multiple ABL1 kinase domain mutations receiving tyrosine kinase inhibitor therapy.
A. Quintas-Cardama, H. Kantarjian, S. O'Brien, E. Jabbour, G. Borthakur, F. Ravandi, S. Verstovsek, J. Shan, and J. Cortes (2011)
Haematologica 96, 918-924
   Abstract »    Full Text »    PDF »
Dasatinib enhances megakaryocyte differentiation but inhibits platelet formation.
A. Mazharian, C. Ghevaert, L. Zhang, S. Massberg, and S. P. Watson (2011)
Blood 117, 5198-5206
   Abstract »    Full Text »    PDF »
Phase II Study of Dasatinib in Relapsed or Refractory Chronic Lymphocytic Leukemia.
P. C. Amrein, E. C. Attar, T. Takvorian, E. P. Hochberg, K. K. Ballen, K. M. Leahy, D. C. Fisher, A. S. LaCasce, E. D. Jacobsen, P. Armand, et al. (2011)
Clin. Cancer Res. 17, 2977-2986
   Abstract »    Full Text »    PDF »
Prognostic significance of treatment response in CML in view of current recommendations for treatment and monitoring.
N. von Bubnoff (2011)
Therapeutic Advances in Hematology 2, 95-110
   Abstract »    PDF »
Dasatinib Treatment for Imatinib Resistant or Intolerant Patients with Chronic Myeloid Leukaemia.
J. Li, G. Xu, S. Yu, L. He, and L. Guo (2011)
Journal of International Medical Research 39, 337-347
   Abstract »    PDF »
Chemotherapeutic agents circumvent emergence of dasatinib-resistant BCR-ABL kinase mutations in a precise mouse model of Philadelphia chromosome-positive acute lymphoblastic leukemia.
N. Boulos, H. L. Mulder, C. R. Calabrese, J. B. Morrison, J. E. Rehg, M. V. Relling, C. J. Sherr, and R. T. Williams (2011)
Blood 117, 3585-3595
   Abstract »    Full Text »    PDF »
Global Phosphoproteomics Reveals Crosstalk Between Bcr-Abl and Negative Feedback Mechanisms Controlling Src Signaling.
L. Rubbi, B. Titz, L. Brown, E. Galvan, E. Komisopoulou, S. S. Chen, T. Low, M. Tahmasian, B. Skaggs, M. Muschen, et al. (2011)
Science Signaling 4, ra18
   Abstract »    Full Text »    PDF »
Pediatric Phase I Trial and Pharmacokinetic Study of Dasatinib: A Report From the Children's Oncology Group Phase I Consortium.
R. Aplenc, S. M. Blaney, L. C. Strauss, F. M. Balis, S. Shusterman, A. M. Ingle, S. Agrawal, J. Sun, J. J. Wright, and P. C. Adamson (2011)
J. Clin. Oncol. 29, 839-844
   Abstract »    Full Text »    PDF »
C-KIT mutation cooperates with full-length AML1-ETO to induce acute myeloid leukemia in mice.
Y.-Y. Wang, L.-J. Zhao, C.-F. Wu, P. Liu, L. Shi, Y. Liang, S.-M. Xiong, J.-Q. Mi, Z. Chen, R. Ren, et al. (2011)
PNAS 108, 2450-2455
   Abstract »    Full Text »    PDF »
NCCN Task Force Report: Tyrosine Kinase Inhibitor Therapy Selection in the Management of Patients With Chronic Myelogenous Leukemia.
S. O'Brien, E. Berman, J. O. Moore, J. Pinilla-Ibarz, J. P. Radich, P. J. Shami, B. D. Smith, D. S. Snyder, H. M. Sundar, M. Talpaz, et al. (2011)
J Natl Compr Canc Netw 9, S-1-S-25
   Abstract »    Full Text »    PDF »
Targeting the BCR-ABL Signaling Pathway in Therapy-Resistant Philadelphia Chromosome-Positive Leukemia.
T. O'Hare, M. W. N. Deininger, C. A. Eide, T. Clackson, and B. J. Druker (2011)
Clin. Cancer Res. 17, 212-221
   Abstract »    Full Text »    PDF »
Extensive pleural and pericardial effusion in chronic myeloid leukemia during treatment with dasatinib at 100 mg or 50 mg daily.
M.-T. Krauth, S. Herndlhofer, M.-T. Schmook, G. Mitterbauer-Hohendanner, E. Schlogl, and P. Valent (2011)
Haematologica 96, 163-166
   Abstract »    Full Text »    PDF »
FLT3 as a therapeutic target in AML: still challenging after all these years.
T. Kindler, D. B. Lipka, and T. Fischer (2010)
Blood 116, 5089-5102
   Abstract »    Full Text »    PDF »
Integrated Microfluidic and Imaging Platform for a Kinase Activity Radioassay to Analyze Minute Patient Cancer Samples.
C. Fang, Y. Wang, N. T. Vu, W.-Y. Lin, Y.-T. Hsieh, L. Rubbi, M. E. Phelps, M. Muschen, Y.-M. Kim, A. F. Chatziioannou, et al. (2010)
Cancer Res. 70, 8299-8308
   Abstract »    Full Text »    PDF »
Properties of CD34+ CML stem/progenitor cells that correlate with different clinical responses to imatinib mesylate.
X. Jiang, D. Forrest, F. Nicolini, A. Turhan, J. Guilhot, C. Yip, T. Holyoake, H. Jorgensen, K. Lambie, K. M. Saw, et al. (2010)
Blood 116, 2112-2121
   Abstract »    Full Text »    PDF »
Activity of the multitargeted kinase inhibitor, AT9283, in imatinib-resistant BCR-ABL-positive leukemic cells.
R. Tanaka, M. S. Squires, S. Kimura, A. Yokota, R. Nagao, T. Yamauchi, M. Takeuchi, H. Yao, M. Reule, T. Smyth, et al. (2010)
Blood 116, 2089-2095
   Abstract »    Full Text »    PDF »
First report of phase 2 study of dasatinib with hyper-CVAD for the frontline treatment of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia.
F. Ravandi, S. O'Brien, D. Thomas, S. Faderl, D. Jones, R. Garris, S. Dara, J. Jorgensen, P. Kebriaei, R. Champlin, et al. (2010)
Blood 116, 2070-2077
   Abstract »    Full Text »    PDF »
Imatinib Upregulates Compensatory Integrin Signaling in a Mouse Model of Gastrointestinal Stromal Tumor and Is More Effective When Combined with Dasatinib.
F. Rossi, Y. Yozgat, E. de Stanchina, D. Veach, B. Clarkson, K. Manova, F. G. Giancotti, C. R. Antonescu, and P. Besmer (2010)
Mol. Cancer Res. 8, 1271-1283
   Abstract »    Full Text »    PDF »
A Novel FRET-Based Biosensor for the Measurement of BCR-ABL Activity and Its Response to Drugs in Living Cells.
T. Mizutani, T. Kondo, S. Darmanin, M. Tsuda, S. Tanaka, M. Tobiume, M. Asaka, and Y. Ohba (2010)
Clin. Cancer Res. 16, 3964-3975
   Abstract »    Full Text »    PDF »
Critical roles for mTORC2- and rapamycin-insensitive mTORC1-complexes in growth and survival of BCR-ABL-expressing leukemic cells.
N. Carayol, E. Vakana, A. Sassano, S. Kaur, D. J. Goussetis, H. Glaser, B. J. Druker, N. J. Donato, J. K. Altman, S. Barr, et al. (2010)
PNAS 107, 12469-12474
   Abstract »    Full Text »    PDF »
Heterogeneity in chronic myeloid leukaemia dynamics during imatinib treatment: role of immune responses.
D. Wodarz (2010)
Proc R Soc B 277, 1875-1880
   Abstract »    Full Text »    PDF »
Discovery of a small-molecule type II inhibitor of wild-type and gatekeeper mutants of BCR-ABL, PDGFR{alpha}, Kit, and Src kinases: novel type II inhibitor of gatekeeper mutants.
E. Weisberg, H. G. Choi, A. Ray, R. Barrett, J. Zhang, T. Sim, W. Zhou, M. Seeliger, M. Cameron, M. Azam, et al. (2010)
Blood 115, 4206-4216
   Abstract »    Full Text »    PDF »
Activity of the Aurora Kinase Inhibitor VX-680 against Bcr/Abl-Positive Acute Lymphoblastic Leukemias.
F. Fei, S. Stoddart, J. Groffen, and N. Heisterkamp (2010)
Mol. Cancer Ther. 9, 1318-1327
   Abstract »    Full Text »    PDF »
A Non-ATP-Competitive Dual Inhibitor of JAK2V617F and BCR-ABLT315I Kinases: Elucidation of a Novel Therapeutic Spectrum Based on Substrate Competitive Inhibition.
S. S. Jatiani, S. C. Cosenza, M. V. R. Reddy, J. H. Ha, S. J. Baker, A. K. Samanta, M. J. Olnes, L. Pfannes, E. M. Sloand, R. B. Arlinghaus, et al. (2010)
Genes & Cancer 1, 331-345
   Abstract »    Full Text »    PDF »
Polo-like Kinase 1 (Plk1) as a Novel Drug Target in Chronic Myeloid Leukemia: Overriding Imatinib Resistance with the Plk1 Inhibitor BI 2536.
K. V. Gleixner, V. Ferenc, B. Peter, A. Gruze, R. A. Meyer, E. Hadzijusufovic, S. Cerny-Reiterer, M. Mayerhofer, W. F. Pickl, C. Sillaber, et al. (2010)
Cancer Res. 70, 1513-1523
   Abstract »    Full Text »    PDF »
Dasatinib Inhibits the Growth of Molecularly Heterogeneous Myeloid Leukemias.
B. S. Guerrouahen, M. Futami, C. Vaklavas, J. Kanerva, Z. L. Whichard, K. Nwawka, E. G. Blanchard, F. Y. Lee, L. J. Robinson, R. Arceci, et al. (2010)
Clin. Cancer Res. 16, 1149-1158
   Abstract »    Full Text »    PDF »
BCR-ABL Gene Expression Is Required for Its Mutations in a Novel KCL-22 Cell Culture Model for Acquired Resistance of Chronic Myelogenous Leukemia.
H. Yuan, Z. Wang, C. Gao, W. Chen, Q. Huang, J.-K. Yee, R. Bhatia, and W. Chen (2010)
J. Biol. Chem. 285, 5085-5096
   Abstract »    Full Text »    PDF »
Potent, transient inhibition of BCR-ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib.
N. P. Shah, D.-W. Kim, H. Kantarjian, P. Rousselot, P. E. D. Llacer, A. Enrico, J. Vela-Ojeda, R. T. Silver, H. J. Khoury, M. C. Muller, et al. (2010)
Haematologica 95, 232-240
   Abstract »    Full Text »    PDF »
Antitumor Activity of Targeting Src Kinases in Endothelial and Myeloid Cell Compartments of the Tumor Microenvironment.
W. Liang, M. Kujawski, J. Wu, J. Lu, A. Herrmann, S. Loera, Y. Yen, F. Lee, H. Yu, W. Wen, et al. (2010)
Clin. Cancer Res. 16, 924-935
   Abstract »    Full Text »    PDF »
Results of Dasatinib Therapy in Patients With Early Chronic-Phase Chronic Myeloid Leukemia.
J. E. Cortes, D. Jones, S. O'Brien, E. Jabbour, F. Ravandi, C. Koller, G. Borthakur, B. Walker, W. Zhao, J. Shan, et al. (2010)
J. Clin. Oncol. 28, 398-404
   Abstract »    Full Text »    PDF »
Selecting optimal second-line tyrosine kinase inhibitor therapy for chronic myeloid leukemia patients after imatinib failure: does the BCR-ABL mutation status really matter?.
S. Branford, J. V. Melo, and T. P. Hughes (2009)
Blood 114, 5426-5435
   Abstract »    Full Text »    PDF »
Mechanisms of Resistance to Imatinib and Second-Generation Tyrosine Inhibitors in Chronic Myeloid Leukemia.
D. Milojkovic and J. Apperley (2009)
Clin. Cancer Res. 15, 7519-7527
   Abstract »    Full Text »    PDF »
Chronic Myeloid Leukemia: An Update of Concepts and Management Recommendations of European LeukemiaNet.
M. Baccarani, J. Cortes, F. Pane, D. Niederwieser, G. Saglio, J. Apperley, F. Cervantes, M. Deininger, A. Gratwohl, F. Guilhot, et al. (2009)
J. Clin. Oncol. 27, 6041-6051
   Abstract »    Full Text »    PDF »
Fine-tuning targeted therapy of CML.
N. P. Shah (2009)
Blood 114, 4914-4915
   Full Text »    PDF »
Nilotinib for the frontline treatment of Ph+ chronic myeloid leukemia.
G. Rosti, F. Palandri, F. Castagnetti, M. Breccia, L. Levato, G. Gugliotta, A. Capucci, M. Cedrone, C. Fava, T. Intermesoli, et al. (2009)
Blood 114, 4933-4938
   Abstract »    Full Text »    PDF »
Personalized Cancer Therapy With Selective Kinase Inhibitors: An Emerging Paradigm in Medical Oncology.
U. McDermott and J. Settleman (2009)
J. Clin. Oncol. 27, 5650-5659
   Abstract »    Full Text »    PDF »
The use of nilotinib or dasatinib after failure to 2 prior tyrosine kinase inhibitors: long-term follow-up.
R. J. Garg, H. Kantarjian, S. O'Brien, A. Quintas-Cardama, S. Faderl, Z. Estrov, and J. Cortes (2009)
Blood 114, 4361-4368
   Abstract »    Full Text »    PDF »
Identifying genotype-dependent efficacy of single and combined PI3K- and MAPK-pathway inhibition in cancer.
M. L. Sos, S. Fischer, R. Ullrich, M. Peifer, J. M. Heuckmann, M. Koker, S. Heynck, I. Stuckrath, J. Weiss, F. Fischer, et al. (2009)
PNAS 106, 18351-18356
   Abstract »    Full Text »    PDF »
Acute dasatinib exposure commits Bcr-Abl-dependent cells to apoptosis.
J. L. Snead, T. O'Hare, L. T. Adrian, C. A. Eide, T. Lange, B. J. Druker, and M. W. Deininger (2009)
Blood 114, 3459-3463
   Abstract »    Full Text »    PDF »
Chronic Myelogenous Leukemia.
S. O'Brien, E. Berman, H. Borghaei, D. J. DeAngelo, M. P. Devetten, S. Devine, H. P. Erba, J. Gotlib, M. Jagasia, J. O. Moore, et al. (2009)
J Natl Compr Canc Netw 7, 984-1023
   Abstract »    PDF »
Long-term outcome of patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors after imatinib failure is predicted by the in vitro sensitivity of BCR-ABL kinase domain mutations.
E. Jabbour, D. Jones, H. M. Kantarjian, S. O'Brien, C. Tam, C. Koller, J. A. Burger, G. Borthakur, W. G. Wierda, and J. Cortes (2009)
Blood 114, 2037-2043
   Abstract »    Full Text »    PDF »
Philadelphia-positive patients who already harbor imatinib-resistant Bcr-Abl kinase domain mutations have a higher likelihood of developing additional mutations associated with resistance to second- or third-line tyrosine kinase inhibitors.
S. Soverini, A. Gnani, S. Colarossi, F. Castagnetti, E. Abruzzese, S. Paolini, S. Merante, E. Orlandi, S. de Matteis, A. Gozzini, et al. (2009)
Blood 114, 2168-2171
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Fyn and Src Are Effectors of Oncogenic Epidermal Growth Factor Receptor Signaling in Glioblastoma Patients.
K. V. Lu, S. Zhu, A. Cvrljevic, T. T. Huang, S. Sarkaria, D. Ahkavan, J. Dang, E. B. Dinca, S. B. Plaisier, I. Oderberg, et al. (2009)
Cancer Res. 69, 6889-6898
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The new tyrosine-kinase inhibitor and anticancer drug dasatinib reversibly affects platelet activation in vitro and in vivo.
M.-P. Gratacap, V. Martin, M.-C. Valera, S. Allart, C. Garcia, P. Sie, C. Recher, and B. Payrastre (2009)
Blood 114, 1884-1892
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Proteasome Inhibition Causes Regression of Leukemia and Abrogates BCR-ABL-Induced Evasion of Apoptosis in Part through Regulation of Forkhead Tumor Suppressors.
Z. Jagani, K. Song, J. L. Kutok, M. R. Dewar, A. Melet, T. Santos, A. Grassian, S. Ghaffari, C. Wu, R. Ren, et al. (2009)
Cancer Res. 69, 6546-6555
   Abstract »    Full Text »    PDF »
Kinome Profiling of Chondrosarcoma Reveals Src-Pathway Activity and Dasatinib as Option for Treatment.
Y. M. Schrage, I. H. Briaire-de Bruijn, N. F.C.C. de Miranda, J. van Oosterwijk, A. H.M. Taminiau, T. van Wezel, P. C.W. Hogendoorn, and J. V.M.G. Bovee (2009)
Cancer Res. 69, 6216-6222
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Dasatinib in the Treatment of Chronic Myeloid Leukemia in Accelerated Phase After Imatinib Failure: The START A Trial.
J. F. Apperley, J. E. Cortes, D.-W. Kim, L. Roy, G. J. Roboz, G. Rosti, E. O. Bullorsky, E. Abruzzese, A. Hochhaus, D. Heim, et al. (2009)
J. Clin. Oncol. 27, 3472-3479
   Abstract »    Full Text »    PDF »
Phase 3 study of dasatinib 140 mg once daily versus 70 mg twice daily in patients with chronic myeloid leukemia in accelerated phase resistant or intolerant to imatinib: 15-month median follow-up.
H. Kantarjian, J. Cortes, D.-W. Kim, P. Dorlhiac-Llacer, R. Pasquini, J. DiPersio, M. C. Muller, J. P. Radich, H. J. Khoury, N. Khoroshko, et al. (2009)
Blood 113, 6322-6329
   Abstract »    Full Text »    PDF »
Discovery and Exploitation of Inhibitor-resistant Aurora and Polo Kinase Mutants for the Analysis of Mitotic Networks.
P. J. Scutt, M. L. H. Chu, D. A. Sloane, M. Cherry, C. R. Bignell, D. H. Williams, and P. A. Eyers (2009)
J. Biol. Chem. 284, 15880-15893
   Abstract »    Full Text »    PDF »
Combination Therapies against Chronic Myeloid Leukemia: Short-term versus Long-term Strategies.
N. L. Komarova and D. Wodarz (2009)
Cancer Res. 69, 4904-4910
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Identification of tyrosine kinase, HCK, and tumor suppressor, BIN1, as potential mediators of AHI-1 oncogene in primary and transformed CTCL cells.
E. Kennah, A. Ringrose, L. L. Zhou, S. Esmailzadeh, H. Qian, M.-w. Su, Y. Zhou, and X. Jiang (2009)
Blood 113, 4646-4655
   Abstract »    Full Text »    PDF »
Once-Daily Dasatinib for Treatment of Patients with Chronic Myeloid Leukemia.
T. Tyler (2009)
Annals of Pharmacotherapy 43, 920-927
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FMS-Like Tyrosine Kinase 3-Internal Tandem Duplication Tyrosine Kinase Inhibitors Display a Nonoverlapping Profile of Resistance Mutations In vitro.
N. von Bubnoff, R. A. Engh, E. Aberg, J. Sanger, C. Peschel, and J. Duyster (2009)
Cancer Res. 69, 3032-3041
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Brain Accumulation of Dasatinib Is Restricted by P-Glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2) and Can Be Enhanced by Elacridar Treatment.
J. S. Lagas, R. A.B. van Waterschoot, V. A.C.J. van Tilburg, M. J. Hillebrand, N. Lankheet, H. Rosing, J. H. Beijnen, and A. H. Schinkel (2009)
Clin. Cancer Res. 15, 2344-2351
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Equally Potent Inhibition of c-Src and Abl by Compounds that Recognize Inactive Kinase Conformations.
M. A. Seeliger, P. Ranjitkar, C. Kasap, Y. Shan, D. E. Shaw, N. P. Shah, J. Kuriyan, and D. J. Maly (2009)
Cancer Res. 69, 2384-2392
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