Optimizing ATR Inhibition and Cisplatin Synergy in Ewing Sarcoma

• Published in: Clinical cancer research Vol. 30; no. 16; pp. 3358 - 3360
• Main Authors: Ohmura, Shunya, Grünewald, Thomas G P
• Format: Journal Article
• Language: English
• Published: United States 15-08-2024
• Subjects: Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Ataxia Telangiectasia Mutated Proteins - antagonists & inhibitors; Ataxia Telangiectasia Mutated Proteins - genetics; Bone Neoplasms - drug therapy; Bone Neoplasms - genetics; Bone Neoplasms - pathology; Cisplatin - pharmacology; Cisplatin - therapeutic use; Drug Synergism; Humans; Oncogene Proteins, Fusion - antagonists & inhibitors; Oncogene Proteins, Fusion - genetics; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Proto-Oncogene Protein c-fli-1 - genetics; Proto-Oncogene Protein c-fli-1 - metabolism; RNA-Binding Protein EWS - antagonists & inhibitors; RNA-Binding Protein EWS - genetics; Sarcoma, Ewing - drug therapy; Sarcoma, Ewing - genetics; Sarcoma, Ewing - pathology
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-24-1047

EWSR1::FLI1-mediated dysregulation of cellular machinery opens up potential new avenues for Ewing sarcoma treatment. A recent study demonstrates that pharmacologic ATR kinase inhibition dramatically synergizes with low-dose cisplatin through EWSR1::FLI1-dependent rewiring of transcription, DNA repair, and translation machinery, which could maximize the therapeutic window of the combinatory therapy. See related article by Jess et al., p. 3533.