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1篇 您的检索式:作者名="Steven ABuck"
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1Inhibition of CDK9 by voruciclib synergistically enhances cell death induced by the Bcl-2 selective inhibitor venetoclax in preclinical models of acute myeloid leukemia显示文摘Venetoclax,an FDA-approved Bcl-2 selective inhibitor for the treatment of chronic lymphocytic leukemia and acute myeloid leukemia(AML),is tolerated well in elderly patients with AML and has good overall response rates;however,resistance remains a concern.In this study,we show that targeting CDK9 with voruciclib in combination with venetoclax results in synergistic antileukemic activity against AML cell lines and primary patient samples.CDK9 inhibition enhances venetoclax activity through downregulation of Mcl-1 and c-Myc.However,downregulation of Mcl-1 is transient,which necessitates an intermittent treatment schedule to allow for repeated downregulation of Mcl-1.Accordingly,an every other day schedule of the CDK9 inhibitor is effective in vitro and in vivo in enhancing the efficacy of venetoclax.Our preclinical data provide a rationale for an intermittent drug administration schedule for the clinical evaluation of the combination treatment for AML.Daniel A.Luedtke Yongwei Su Jun Ma Xinyu Li Steven ABuck Holly Edwards Lisa Polin Juiwanna Kushner Sijana HDzinic Kathryn White Hai Lin Jeffrey WTaub Yubin Ge 2020Signal Transduction and Targeted Therapy2020,5,1:3
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