Elimusertib has anti-tumor activity in preclinical patient-derived pediatric solid tumor models Journal Article
| Authors: | Pusch, F. F.; García, H. D.; Xu, R.; Görgen, D.; Bei, Y.; Bröckner, L.; Röefzaad, C.; Von Stebut, J.; Bardinet, V.; Gonzalez, R. C.; Eggert, A.; Schulte, J. H.; Hundsdörfer, P.; Seifert, G.; Haase, K.; Schäfer, B. W.; Wachtel, M.; Köhl, A. A.; Ortiz, M. V.; Wengner, A. M.; Scheer, M.; Henssen, A. G. |
| Article Title: | Elimusertib has anti-tumor activity in preclinical patient-derived pediatric solid tumor models |
| 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 anti-Tumor 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 anti-Tumor effects than some standard of care chemotherapies, particularly in alveolar rhabdomysarcoma PDX. Thus, elimusertib has strong preclinical anti-Tumor activity in pediatric solid tumor models, which may translate to clinically meaningful responses in patients. © 2024 American Association for Cancer Research Inc.. All rights reserved. |
| Keywords: | immunohistochemistry; cancer chemotherapy; child; controlled study; protein expression; protein phosphorylation; human cell; overall survival; monotherapy; nonhuman; patient selection; solid tumor; antineoplastic agents; antineoplastic agent; neoplasm; neoplasms; biomarkers; biological marker; mouse; dna damage; progression free survival; protein kinase inhibitor; animal experiment; animal model; practice guideline; in vivo study; antineoplastic activity; in vitro study; tumor xenograft; drug screening; pathology; xenograft model antitumor assays; cell line, tumor; ewing sarcoma; protein kinase inhibitors; neuroblastoma; genomic instability; tumor cell line; organization; single stranded dna; tumor growth; rhabdomyosarcoma; fluorescence activated cell sorting; pediatric oncology; embryonal rhabdomyosarcoma; nucleic acid structure; body weight loss; g2 phase cell cycle checkpoint; humans; human; female; article; whole exome sequencing; atr inhibitor; patient-derived xenograft.; elimusertib; rh41 cell line |
| Journal Title: | Molecular Cancer Therapeutics |
| Volume: | 23 |
| Issue: | 4 |
| ISSN: | 1535-7163 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2024-04-01 |
| Start Page: | 507 |
| End Page: | 519 |
| Language: | English |
| DOI: | 10.1158/1535-7163.Mct-23-0094 |
| PUBMED: | 38159110 |
| PROVIDER: | scopus |
| PMCID: | PMC10985474 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
