Elimusertib has Antitumor Activity in Preclinical Patient-Derived Pediatric Solid Tumor Models
Fabian F Pusch1,2, Heathcliff Dorado García1,2, Robin Xu1,2
1Experimental and Clinical Research Center (ECRC) of the MDC and Charité Berlin, Berlin, Germany.
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.
Insights
Elimusertib, an ATR inhibitor, shows significant preclinical antitumor activity in pediatric solid tumors. This novel therapy demonstrated superior efficacy compared to some standard chemotherapies in preclinical models.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Ataxia telangiectasia and Rad3-related protein (ATR) inhibitors are emerging cancer therapeutics.
- The clinical efficacy of elimusertib is under investigation, but its preclinical activity in pediatric cancers is not well-established.
Purpose of the Study:
- To evaluate the preclinical antitumor activity of elimusertib in pediatric solid tumor models.
- To identify potential response biomarkers for elimusertib therapy.
Main Methods:
- Assessed elimusertib activity in 38 pediatric cancer cell lines and 32 patient-derived xenograft (PDX) models.
- Conducted in vitro and in vivo molecular characterization of treated models.
Main Results:
- Elimusertib demonstrated pronounced objective response rates as monotherapy in PDX models.
- Elimusertib exhibited stronger antitumor effects than some standard chemotherapies, notably in alveolar rhabdomysarcoma PDX models.
Conclusions:
- Elimusertib possesses significant preclinical antitumor activity against pediatric solid tumors.
- These findings suggest elimusertib's potential for clinically meaningful responses in pediatric cancer patients.
