Helmholtz Gemeinschaft


Elimusertib has antitumor activity in preclinical patient-derived pediatric solid tumor models

PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
[img] Other (Supplementary Data)

Item Type:Article
Title:Elimusertib has antitumor activity in preclinical patient-derived pediatric solid tumor models
Creators Name:Pusch, F.F. and Dorado Garcia, H. and Xu, R. and Gürgen, D. and Bei, Y. and Brückner, L. and Röefzaad, C. and von Stebut, J. and Bardinet, V. and Chamorro Gonzalez, R. and Eggert, A. and Schulte, J.H. and Hundsdörfer, P. and Seifert, G. and Haase, K. and Schäfer, B.W. and Wachtel, M. and Kühl, A.A. and Ortiz, M.V. and Wengner, A.M. and Scheer, M. and Henssen, A.G.
Abstract:he 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.
Keywords:Pediatric Oncology, ATR Inhibitor, Rhabdomyosarcoma, Neuroblastoma, Patient-Derived Xenograft
Source:Molecular Cancer Therapeutics
Publisher:American Association for Cancer Research
Page Range:507-519
Date:2 April 2024
Official Publication:https://doi.org/10.1158/1535-7163.MCT-23-0094
PubMed:View item in PubMed

Repository Staff Only: item control page


Downloads per month over past year

Open Access
MDC Library