Federal Cooperative Agreement Summary

Auburn University received a $317,704 Cooperative Agreement award from the National Cancer Institute (NCI) under the Cancer Cause and Prevention Research program (CFDA 93.393), effective July 9, 2026 through June 30, 2029. The award funds research to develop novel pan-RAS (Rat Sarcoma) inhibitors derived from natural products for colorectal cancer interception. The research integrates high-throughput screening (HTS) of the NCI natural product library with advanced analytical and computational tools to identify compounds with selective antiproliferative activity against RAS-mutant cancer cells. Deliverables include execution of cell-based HTS assays using isogenic colorectal cancer cell lines, secondary screening to assess RAS pathway inhibition and apoptosis induction, and application of affinity selection mass spectrometry coupled with machine learning to rank and characterize lead compounds based on potency and selectivity.

The project addresses a significant clinical need: RAS mutations drive approximately 30% of all cancers and up to 50% of colorectal cancer cases, yet existing FDA-approved mutant-specific KRAS inhibitors have limited preventive utility due to mutation heterogeneity and compensatory signaling. By developing a pan-RAS inhibitor capable of selectively eliminating premalignant adenoma cells, the research aims to block colorectal cancer at its earliest stage. Auburn University will coordinate screening and characterization activities, with NCATS (National Center for Advancing Translational Sciences) providing sub-fractionated and purified compounds for downstream testing.