Erschienen in:
27.03.2021 | Progress in Hematology
Target spectrum of the BCR-ABL tyrosine kinase inhibitors in chronic myeloid leukemia
verfasst von:
Hyewon Lee, Igor Novitzky Basso, Dennis Dong Hwan Kim
Erschienen in:
International Journal of Hematology
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Ausgabe 5/2021
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Abstract
BCR-ABL1 plays a key role in the pathogenesis of chronic myeloid leukemia (CML), and it has been investigated as a druggable target of tyrosine kinase inhibitors (TKIs) over two decades. Since imatinib, the first TKI for anti-cancer therapy, was successfully applied in CML therapy, further generation TKIs and a novel allosteric inhibitor targeting the myristate binding site have been developed as alternative options for CML management. However, significant concerns regarding toxicity profiles, especially in long-term treatment, have emerged from TKI clinical data. Efforts to reduce adverse events and serious complications are warranted not only for survival, but also quality of life in CML patients. A better understanding of the mechanism of action will help to identify on- and off-target effects of TKIs, and guide personalized TKI drug selection in each individual CML patient. Herein, this review summarizes the biologic mechanism of BCR-ABL1 inhibition and differential target spectra, and related off-target effects of each TKI.