Federal Project Grant Award Summary

St. Jude Children's Research Hospital Inc. received a $647,502 Project Grant award from the National Cancer Institute under the Cancer Treatment Research program (CFDA 93.395), effective July 1, 2026, through June 30, 2031. The award funds research to develop small molecule inhibitors targeting DDX19A, an RNA helicase identified as a critical genomic dependency in Ewing sarcoma, an aggressive pediatric bone malignancy. The research applies state-of-the-art functional genomic, epigenomic, and proteomic approaches to interrogate how DDX19A regulates gene expression programs controlled by the EWS/FLI oncoprotein, with the objective of demonstrating that DDX19A inhibition induces therapeutic toxicity through transcriptional overload and cell death.

The deliverables include mechanistic characterization of DDX19A's role in constraining transcriptional and epigenetic programs in Ewing sarcoma cells, coupled with medicinal chemistry optimization to develop potent and selective allosteric inhibitors of DDX19A as potential therapeutic agents. This project advances the Cancer Treatment Research program's mission to develop improved cancer treatment methods through discovery and development of molecularly targeted therapies, with particular emphasis on addressing master transcription factors that drive oncogenic programs in pediatric malignancies.