Federal Project Grant Award Summary

The University of Texas Southwestern Medical Center received a $376,886 Project Grant from the National Cancer Institute (NCI) under the Cancer Treatment Research program (CFDA 93.395) for the period July 1, 2026 through June 30, 2029. The award supports the development of novel small-molecule inhibitors targeting Site-One Protease (S1P) to prevent and treat cancers, particularly clear cell renal cell carcinoma and hepatocellular carcinoma. The research builds on the investigator team's recent discovery that a co-factor protein called SREBP Regulating Gene (SPRING) activates S1P and enables purification of the enzyme in its active form. The project aims to synthesize and evaluate tool molecules that will clarify the functional scope of SPRING in S1P activation and advance the translational potential of S1P inhibitors as cancer therapeutics.

This research directly addresses a critical cancer cell vulnerability by targeting lipid overproduction, a hallmark of malignant cells required for rapid growth and survival signaling. Building upon prior structural characterization work with the experimental inhibitor PF-429242, the funded project will generate molecular tools necessary to resolve outstanding mechanistic questions about SPRING-S1P interactions and establish a pipeline for clinically viable inhibitor candidates. The Cancer Treatment Research program supports discovery through clinical development of novel cancer therapies across all modalities; this award exemplifies the program's emphasis on molecular and biological therapy innovation to improve treatment outcomes.