Preclinical evaluation of the combination of AZD1775 and irinotecan against selected pediatric solid tumors: A Pediatric Preclinical Testing Consortium report.

ABSTRACT:

Introduction

WEE1 is a serine kinase central to the G₂ checkpoint. Inhibition of WEE1 can lead to cell death by permitting cell-cycle progression despite unrepaired DNA damage. AZD1775 is a WEE1 inhibitor that is in clinical development for children and adults with cancer.

Methods

AZD1775 was tested using a dose of 120 mg/kg administered orally for days 1 to 5. Irinotecan was administered intraperitoneally at a dose of 2.5 mg/kg for days 1 to 5 (one hour after AZD1775 when used in combination). AZD1775 and irinotecan were studied alone and in combination in neuroblastoma (n = 3), osteosarcoma (n = 4), and Wilms tumor (n = 3) xenografts.

Results

AZD1775 as a single agent showed little activity. Irinotecan induced objective responses in two neuroblastoma line

SUBMITTER: Kolb EA 

PROVIDER: S-EPMC8752046 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature