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    11ms
    Role of CDK8/19 inhibition in sensitization of chronic myelogenous leukemia cells to Bcr-Abl antagonists (EACR 2023)
    Selective inhibitors of Bcr-Abl (prototype – imatinib mesylate, IM, Gleevec®) cause a therapeutic effect in the treatment of the primary process...Senexin B (SenB) and SNX631 were used for selective inhibition of CDK8/19, to suppress Bcr-Abl – IM, dasatinib, nilotinib, PF-114.Results and DiscussionsIt was found that CDK8/19 inhibition by SenB alone does not have an antiproliferative effect on CML cells...These changes were not demonstrated in KU812, where neither SenB sensitization, nor changes in expression of CKIs and c-Myc level were detected.ConclusionInhibition of CDK8/19 helps to overcome the delay of the cell cycle caused by the Bcr-Abl antagonist in CML cells and increase the death of tumor cells. The absence of general toxicity of CDK8/19 inhibitors during prolonged treatment under experimental conditions allows us to recommend CDK8/19 inhibition with targeted therapy of Bcr-Abl-positive tumors in prospect.
    PARP Biomarker
    |
    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CASP9 (Caspase 9) • CDK9 (Cyclin Dependent Kinase 9) • CDKN2C (Cyclin Dependent Kinase Inhibitor 2C)
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    MYC expression • CDKN1B expression
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    dasatinib • imatinib • Tasigna (nilotinib) • SNX-631 • PF-114 • Senexin B
    over2years
    Novel BCR-ABL1 tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia. (PubMed, Expert Rev Hematol)
    No abstract available
    Journal
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    ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase)
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    Scemblix (asciminib) • Nailike (olverembatinib) • Hansoh Xinfu (flumatinib) • PF-114 • vodobatinib (SCO - 088)