Abstract
The addition of molecularly targeted therapies to current chemotherapy regimens may improve acute lymphoblastic leukemia (ALL) outcomes and reduce acute and late toxicities. Checkpoint kinase 1 (CHK1) orchestrates cell cycle checkpoint control in the setting of DNA damage. CHK1 is expressed in both T- and B-ALL and represents a promising therapeutic target. Herein, we show that prexasertib, a targeted CHK1 inhibitor, exhibits significant single-agent efficacy in vivo using ALL patient-derived xenograft (PDX) models and synergizes in vitro with a nucleoside analog. These results support further clinical testing of prexasertib in ALL.
Publication types
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Letter
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Checkpoint Kinase 1 / antagonists & inhibitors*
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Deoxycytidine / analogs & derivatives
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Deoxycytidine / pharmacology
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Deoxycytidine / therapeutic use
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Drug Synergism
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Gemcitabine
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Humans
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Mice
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
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Protein Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / therapeutic use*
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Pyrazines / pharmacology
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Pyrazines / therapeutic use*
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Pyrazoles / pharmacology
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Pyrazoles / therapeutic use*
Substances
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Protein Kinase Inhibitors
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Pyrazines
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Pyrazoles
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prexasertib
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Deoxycytidine
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Checkpoint Kinase 1
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Gemcitabine