Elimusertib Has Antitumor Activity in Preclinical Patient-Derived Pediatric Solid Tumor Models

Overview

Journal Mol Cancer Ther

Date 2023 Dec 30

PMID 38159110

Authors

Fabian F Pusch

Heathcliff Dorado Garcia

Robin Xu

Dennis Gurgen

Yi Bei

Lotte Bruckner

Claudia Roefzaad

Jennifer von Stebut

Victor Bardinet

Rocio Chamorro Gonzalez

Angelika Eggert

Johannes H Schulte

Patrick Hundsdorfer

Georg Seifert

Kerstin Haase

Beat W Schafer

Marco Wachtel

Anja A Kuhl

Michael V Ortiz

Antje M Wengner

Monika Scheer

Anton G Henssen

Affiliations

Soon will be listed here.

Abstract

The small-molecule inhibitor of ataxia telangiectasia and Rad3-related protein (ATR), elimusertib, is currently being tested clinically in various cancer entities in adults and children. Its preclinical antitumor activity in pediatric malignancies, however, is largely unknown. We here assessed the preclinical activity of elimusertib in 38 cell lines and 32 patient-derived xenograft (PDX) models derived from common pediatric solid tumor entities. Detailed in vitro and in vivo molecular characterization of the treated models enabled the evaluation of response biomarkers. Pronounced objective response rates were observed for elimusertib monotherapy in PDX, when treated with a regimen currently used in clinical trials. Strikingly, elimusertib showed stronger antitumor effects than some standard-of-care chemotherapies, particularly in alveolar rhabdomysarcoma PDX. Thus, elimusertib has strong preclinical antitumor activity in pediatric solid tumor models, which may translate to clinically meaningful responses in patients.

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