Abstract A068: Investigation of changes in epithelial cell states in pancreatic cancer using human organoids

Abstract

Abstract Pancreatic cancer is among the deadliest cancers in the US. The low survival rates of pancreatic cancer are mainly due to late diagnosis and a lack of effective treatments. To improve the clinical management of pancreatic cancer, we need better understand the biological mechanisms underlying the initiation and progression of this disease. With a focus on elucidating pancreatic cancer biology in human patients, we have developed organoid models for pancreatic normal physiology and malignancy using pluripotent stem cells or patient tumor tissues. Using stem cell-derived organoids, we investigated the interactions between pancreatic epithelial cell states, oncogenic signaling pathways, and cytokines. In this study, we discovered that human acinar organoids, compared to ductal organoids, were more sensitive to KRasG12D oncogenic signaling in vitro and in vivo, which supported acinar cells as the main cell of origin for pancreatic cancer in human patients. We have also developed working pipelines using organoid models to identify biomarkers and predict patient drug responses. Based on those successful studies, we now focus on investigating biological principles underlying racial disparities in pancreatic cancer using human cell models. Citation Format: Ling Huang, Senthil Muthuswamy. Investigation of changes in epithelial cell states in pancreatic cancer using human organoids [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A068.