This Project Grant award under the National Cancer Institute's (NCI) Cancer Treatment Research program (CFDA 93.395) provides $653,452 to the University of California, Los Angeles (UCLA) to conduct extensive evaluations of patient specimens from a clinical trial investigating the use of a CD73 inhibitor to limit adenosine signaling in the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC). The goal is to define the impact of CD73 inhibition on tumor adenosine metabolism, signaling, and immunosuppression, as well as identify predictors of response and resistance. The project will also utilize preclinical PDAC models and human tumor explants to examine the roles of additional ectonucleotidases ENPP1 and CD39 in regulating ATP breakdown and adenosine generation, and explore whether ENPP1 inhibition can cooperate with CD73 inhibition to enhance anti-tumor STING signaling. This comprehensive, transdisciplinary research effort aims to advance understanding of ATP and adenosine metabolism in the PDAC tumor microenvironment and identify strategies to effectively reverse adenosine-mediated immunosuppression, thereby improving outcomes for patients with this aggressive cancer type.
Generated 2/25/25, 1:46 AM