Preclinical efficacy of prexasertib in acute lymphoblastic leukemia

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.