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| Item Type: | Article |
|---|---|
| Title: | Elimusertib has antitumor activity in preclinical patient-derived pediatric solid tumor models |
| Creators Name: | Pusch, F.F., Dorado Garcia, H., Xu, R., Gürgen, D., Bei, Y., Brückner, L., Röefzaad, C., von Stebut, J., Bardinet, V., Chamorro Gonzalez, R., Eggert, A., Schulte, J.H., Hundsdörfer, P., Seifert, G., Haase, K., Schäfer, B.W., Wachtel, M., Kühl, A.A., Ortiz, M.V., Wengner, A.M., 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 |
| ISSN: | 1535-7163 |
| Publisher: | American Association for Cancer Research |
| Volume: | 23 |
| Number: | 4 |
| 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 |
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