Abstract IA041: Proteomic analyses of cancer models to identify and validate molecular determinants of health disparities
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy that remains refractory to current therapies due in part to adaptive mechanisms of therapeutic resistance and subtype plasticity. Significant racial disparities further complicate PDAC outcomes, as Black patients exhibit higher incidence rates and shorter survival times than White patients even after controlling for socioeconomic and clinical variables. These observations suggest that biologically distinct molecular programs may contribute to aggressive PDAC phenotypes across diverse patient populations. However, current PDAC subtype models were developed primarily using predominantly White patient cohorts, and their generalizability across diverse populations remains poorly understood. Our quantitative proteomic studies identified four PDAC molecular subtypes associated with distinct therapeutic responses and clinical outcomes. Preliminary proteomic analyses further demonstrate that tumors from Black patients are enriched for aggressive inflammatory and Basal-like molecular programs associated with chemoresistance. In addition, we identified the polycomb repressor complex 1 protein RNF2 as elevated in PDAC tumors from Black patients and demonstrate that RNF1/2-dependent epigenetic regulation suppresses the PDAC lineage specification factor GATA6, promotes aggressive subtype plasticity, and contributes to chemotherapy adaptation and emergence of drug-tolerant persister (DTP) states. This study demonstrates that incorporating genetically diverse samples and model systems can improve our understanding of aggressive PDAC biology across patient populations and supports the framework for precision proteomics-guided therapeutic stratification in PDAC. Nicholas T. Woods, Jose Trevino. Proteomic analyses of cancer models to identify and validate molecular determinants of health disparities [abstract]. In: Proceedings of the 19th AACR Conference on the Science of Cancer Health Disparities; 2026 Oct 18-21; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2026;35(10 Suppl):Abstract nr IA041.