Abstract 1531: The role of HDAC1 in pancreatic cancer metabolism

Abstract Pancreatic cancer is a malignant disease often driven by mutations in the KRAS gene. It is associated with significant metabolic reprogramming driving tumor growth, drug resistance, and adaptation in its dense, nutrient-limited tumor microenvironments. To date, the mediators of PDAC metabolism are not fully understood. Analyzing gene expression changes in PDAC tumors compared to normal tissues identified histone deacetylase 1 (HDAC1) as a consistently upregulated gene. We found that HDAC1-high tumors display strong metabolic alterations, including the upregulation of genes in glycolysis and other metabolic processes, and that treatment with Class I selective HDAC inhibitors (HDACi) selectively blunted growth. Initial experiments altering HDAC1 expression transiently in multiple pancreatic cancer cell lines demonstrate alternate metabolic responses. Consistent with existing literature, we observe that HDACi effectively suppressed pancreatic cancer cell growth, primarily class I selective inhibitors. Furthermore, we recently developed HDAC1 knockout cell lines that demonstrate shifts in metabolic profiles of pancreatic cancer and slowed growth rates in HDACi sensitive cell lines through immunoblotting, metabolomics and Seahorse assay. We expect that our findings will show the significance and prospects of targeting HDAC1 in pancreatic cancer therapy and its potential to overcome resistance with current therapeutic. Citation Format: Don-Gerard Cavakiah Blanchard Conde, Evan J. Zhou, Maximillian Farma, Chiamaka J. Ezeh, Laiba Shiekh, Matthew Cheung, Zeribe C. Nwosu, Nwosu Lab, Cornell University. The role of HDAC1 in pancreatic cancer metabolism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1531.