Federal Grant Award Summary

The University of North Carolina at Chapel Hill received a $628,539 Project Grant from the National Cancer Institute under the Cancer Treatment Research program (CFDA 93.395) effective July 1, 2026, through June 30, 2031. This award supports the development of novel small molecule inhibitors targeting the deubiquitinase OTUD7A as a therapeutic strategy for Ewing sarcoma, an aggressive malignancy affecting children and young adults. The research team will utilize structure-based drug design, enzymatic assays, and cell-based assays to develop potent OTUD7A inhibitors and validate their efficacy in mouse models of Ewing sarcoma.

The primary deliverable is the generation of preclinical data supporting advancement of a selective, orally available OTUD7A inhibitor candidate into Good Laboratory Practice (GLP) toxicity studies in multiple species. This work builds upon preliminary findings demonstrating that OTUD7A suppression reduces EWS-FLI1 protein levels and inhibits Ewing sarcoma growth both in vitro and in vivo, and represents a novel approach to controlling protein stability mechanisms of oncogenic fusion proteins applicable to other cancer types. Upon completion, the research is expected to deliver clinical trial-ready candidate compounds with sufficient preclinical validation to support Investigational New Drug (IND) applications.