Abstract Pancreatic cancer is a lethal disease that has a five-year survival rate of ∼13%. Pancreatic cancer is marked by a number of significant alterations in its dense tumor microenvironment and metabolism. Our analyses of differential gene expression in multiple datasets point to HDAC1 as a consistently upregulated gene in pancreatic cancer and one that is significantly correlated with multiple metabolic pathways. Using CRISPR/Cas-9 gene editing, we generated HDAC1-knockout cell lines. Our current findings show when HDAC1 is deleted, pancreatic cancer cell lines display alternate growth phenotypes, differentially express metabolic targets, and have global metabolomics changes. Further, Seahorse analysis revealed a switch to oxidative phosphorylation in a subset of HDAC1 knockout cells. This distinct response to HDAC1 deletion demonstrates the importance of understanding the nuanced characteristics in order to effectively target metabolism in pancreatic cancer based on different patient subgroups. Citation Format: Don-Gerard B. Conde, Evan J. Zhou, Maximilian Farma, Soren Jensen, Laiba Sheikh, Matthew Cheung, Chiamaka J. Ezeh, Harshita N. Khedkar, Zeribe C. Nwosu. Deletion of HDAC1 demonstrates alternative metabolic response in pancreatic cancer abstract. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr B135.
Conde et al. (2025) studied this question.