Preclinical efficacy of prexasertib in acute lymphoblastic leukemia

Jason Ostergaard; Leslie M Jonart; Maryam Ebadi; Stacia L Koppenhafer; David J Gordon; Peter M Gordon

doi:10.1111/bjh.17610

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Preclinical efficacy of prexasertib in acute lymphoblastic leukemia

Journal article

Open access

Peer reviewed

Preclinical efficacy of prexasertib in acute lymphoblastic leukemia

Jason Ostergaard, Leslie M Jonart, Maryam Ebadi, Stacia L Koppenhafer, David J Gordon and Peter M Gordon

British journal of haematology, Vol.194(6), pp.1094-1098

09/2021

DOI: 10.1111/bjh.17610

PMCID: PMC8504167

PMID: 34096630

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https://doi.org/10.1111/bjh.17610View

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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.

Animals

Cell Line, Tumor

Cell Proliferation - drug effects

Checkpoint Kinase 1 - antagonists & inhibitors

Deoxycytidine - analogs & derivatives

Deoxycytidine - pharmacology

Deoxycytidine - therapeutic use

Drug Synergism

Humans

Mice

Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy

Protein Kinase Inhibitors - pharmacology

Protein Kinase Inhibitors - therapeutic use

Pyrazines - pharmacology

Pyrazines - therapeutic use

Pyrazoles - pharmacology

Pyrazoles - therapeutic use

Details

Title: Subtitle: Preclinical efficacy of prexasertib in acute lymphoblastic leukemia
Creators: Jason Ostergaard - University of Minnesota
Leslie M Jonart - University of Minnesota
Maryam Ebadi - University of Minnesota
Stacia L Koppenhafer - University of Iowa
David J Gordon - University of Iowa
Peter M Gordon - University of Minnesota
Resource Type: Journal article
Publication Details: British journal of haematology, Vol.194(6), pp.1094-1098
DOI: 10.1111/bjh.17610
PMID: 34096630
PMCID: PMC8504167
ISSN: 0007-1048
eISSN: 1365-2141
Grant note: R37 CA240846 / NCI NIH HHS R37 CA217910 / NCI NIH HHS
Language: English
Date published: 09/2021
Academic Unit: Stead Family Department of Pediatrics; Hematology/Oncology
Record Identifier: 9984353848202771

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