Abstract LB483: Benchmarking human tumor slices from gastrointestinal malignancies for precision cancer therapy

Abstract Patient-derived tumor slices (PDS) have been used to evaluate drug sensitivity in multiple human tumor types. Despite this, standardized parameters to establish PDS as a precision medicine tool are lacking. Here we benchmarked proliferation rates and standard deviations from 40 gastrointestinal cancer specimens, defining normal biological variation. Here the mean standard deviation rates in pancreatic duct adenocarcinoma (PDAC), appendiceal cancer, and colorectal adenocarcinomas were 10%, 6%, and 15%, respectively. Using these data, we established threshold criteria set at a z-score of 3 standard deviations in order to distinguish meaningful drug sensitivity to the pan-RAS(On) inhibitor RMC-6236, from that of normal biological variation. This framework enabled classification of PDAC and appendiceal PDS cultures as sensitive or resistant. To benchmark the predictive value of slice assays, we compared RAS-inhibitor activity across matched patient-derived organoids (PDOs) and xenografts (PDXs), and further determined that slice-based assay sensitivity predicted sensitivity and survival outcomes in matching orthogonal tumor models. Citation Format: Kevin Gulay, Rithika Medari, Isabella Ng, Jingjing Zou, Ethan Tabibzadeh, Elias Warren, Brian Wishart, Rebekah White, Herve Tiriac, Andrew Lowy, Jonathan Weitz. Benchmarking human tumor slices from gastrointestinal malignancies for precision cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr LB483.