Target spectrum of the BCR-ABL tyrosine kinase inhibitors in chronic myeloid leukemia

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 generatio...

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Bibliographic Details
Published in:International journal of hematology 2021-05, Vol.113 (5), p.632-641
Main Authors: Lee, Hyewon, Basso, Igor Novitzky, Kim, Dennis Dong Hwan
Format: Article
Language:English
Subjects:
Adverse events
Allosteric properties
BCR-ABL protein
Binding sites
Chronic myeloid leukemia
Complications
Fusion protein
Hematology
Imatinib
Inhibitors
Kinases
Leukemia
Medicine
Medicine & Public Health
Myeloid leukemia
Oncology
Pathogenesis
Patients
Progress in Hematology
Quality of life
Target recognition
Toxicity
Tyrosine
Tyrosine kinase inhibitors
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Summary: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.
ISSN:0925-5710
1865-3774
DOI:10.1007/s12185-021-03126-6