Federal Cooperative Agreement Summary

The University of Kansas Medical Center Research Institute, Inc. received a Cooperative Agreement award of $325,454 from the National Cancer Institute (NCI) under the Cancer Cause and Prevention Research program (CFDA 93.393), effective July 7, 2026, through June 30, 2029. The award funds a high-throughput screening (HTS) initiative to identify natural compounds that inhibit BCL9-β-catenin binding interactions as a strategy for breast cancer prevention. During the UG3 phase (months 1-36), the awardee will optimize and validate primary, secondary, and orthogonal HTS assays using a pilot-scale NCI Natural Products library, including AlphaScreen, fluorescence polarization, and cell-based reporter assays. Concurrently, the awardee will develop mechanistic characterization assays encompassing co-immunoprecipitation, cell proliferation, luciferase reporter assays for canonical Wnt signaling, cytotoxicity studies, invasion and migration assays, and mammosphere self-renewal assays to evaluate lead compounds.

The subsequent UH3 phase (months 1-12) involves full-scale HTS screening of a 500,000-compound natural products library at the National Center for Advancing Translational Sciences (NCATS), with top-ranked hits prioritized based on activity, toxicity, chemistry novelty, and selectivity profiles. Leading compounds will be transferred to the principal investigator's laboratory for mechanistic validation using the assays developed in the UG3 phase, with emphasis on efficacy in ductal carcinoma in situ (DCIS) cell lines while excluding cytotoxic compounds and those exhibiting off-target effects. The award includes determination of pharmacokinetics for promising candidates to advance candidates toward preclinical and clinical development for cancer prevention applications.