The National Cancer Institute (NCI) awarded a $710,980 Project Grant under the Cancer Treatment Research program (CFDA 93.395) to Weill Medical College of Cornell University to conduct research on the SPOP ubiquitin signaling pathway and its therapeutic potential in prostate cancer. The five-year project aims to define the mechanistic, biological, and therapeutic consequences of alterations to the SPOP signaling pathway, including its upstream regulator G3BP1, using novel models and human prostate cancer samples. The research will elucidate how modulating SPOP activity reprograms androgen receptor function, making these cancers reliant on androgen receptor activity, and explore the ability to target this axis with small molecule inhibitors as a viable therapeutic strategy. This project supports NCI's broader efforts to develop improved methods of cancer treatment and control the disease in patients.