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Chemotherapy for Leukemia pp 55–75Cite as

Dasatinib, Nilotinib, Bosutinib, Ponatinib, and Other TKIs

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Abstract

ABL tyrosine kinase inhibitor (TKI) imatinib mesylate has led to a marked change in the treatment of chronic myeloid leukemia (CML). However, resistance and intolerance to imatinib are frequently reported, particularly in patients with advanced-stage disease; this leads to around 30% of CML patients discontinuing imatinib treatment. Point mutations within the ABL kinase domain, which interfere with imatinib binding, are the most critical cause of imatinib resistance. To overcome this, the second-generation ATP-competing ABL TKIs such as dasatinib, nilotinib, bosutinib, and bafetinib have been developed. Despite promising clinical results of these, a common mutation, T315I, is not effectively targeted by any of the second-generation ABL TKIs. Therefore, a third-generation ABL TKI, ponatinib, was developed and shows good clinical efficacy against CML cells harboring the T315I mutation. Thus, treatments for CML are progressing rapidly, and further evolution is expected.

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  1. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan

    Shinya Kimura

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  1. University of Fukui, Fukui, Japan

    Takanori Ueda

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Kimura, S. (2017). Dasatinib, Nilotinib, Bosutinib, Ponatinib, and Other TKIs. In: Ueda, T. (eds) Chemotherapy for Leukemia. Springer, Singapore. https://doi.org/10.1007/978-981-10-3332-2_4

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