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Class effects of tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia

Leukemia volume 23, pages 1698–1707 (2009)Cite this article

Abstract

Tyrosine kinase inhibitors have revolutionized the treatment of chronic myeloid leukemia (CML), offering patients several targeted therapeutic options that provide the possibility of sustained remissions and prolonged survival. With the availability of imatinib, nilotinib and dasatinib, physicians must weigh the efficacy and safety profile of each agent when choosing the best therapeutic option for individual patients. Each agent targets tyrosine kinases within the cell uniquely to cause the desired antiproliferative effect. In addition to inhibiting the BCR-ABL kinase, imatinib and nilotinib target the same array of other tyrosine kinases, including c-KIT and platelet-derived growth factor receptor (PDGFR), albeit with differing potencies. While targeting BCR-ABL with the highest potency among approved agents in CML, dasatinib also targets a broad array of off-target kinases, including SRC family members, PDGFR and EPHB4. The differences in kinase inhibition profiles among these agents in vitro probably account for the differing clinical safety profiles of these agents. This paper reviews the various kinases inhibited by imatinib, nilotinib and dasatinib, and describes the potential impact of kinase inhibition on the efficacy and safety of each agent.

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Acknowledgements

Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals. We thank Michael Mandola, PhD (Health Interactions), for medical editorial assistance with this manuscript.

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Authors and Affiliations

  1. Institute for Drug Development, Cancer Therapy and Research Center at the University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    F J Giles & R Swords

  2. Department of Hematology, University College Hospital, Galway, Ireland

    M O'Dwyer

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  1. F J Giles
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  2. M O'Dwyer
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  3. R Swords
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Correspondence to F J Giles.

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Giles, F., O'Dwyer, M. & Swords, R. Class effects of tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia. Leukemia 23, 1698–1707 (2009). https://doi.org/10.1038/leu.2009.111

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  • DOI: https://doi.org/10.1038/leu.2009.111

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