Abstract B45: Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell and patient-derived tumor organoids

摘要: There are few in vitro models of exocrine pancreas development and primary human pancreatic adenocarcinoma (PDAC). We establish three-dimensional culture conditions to induce the differentiation pluripotent stem cells (PSCs) into progenitor organoids that form ductal acinar structures vivo. Expression mutant KRAS or TP53 induces mutation-specific phenotypes TP53R175H induced cytosolic SOX9 localization. In patient tumors bearing mutations, was cytoplasmic associated with mortality. Culture also defined for clonal generation tumor from freshly resected PDAC. Tumor maintain status, histoarchitecture, phenotypic heterogeneity tumor, retain patient-specific physiologic changes including hypoxia, oxygen consumption, epigenetic marks, differential sensitivity EZH2 inhibition. Thus, can be used model PDAC drug screening identify precision therapy strategies. Citation Format: Ling Huang, Audrey Holtzinger, Ishaan Jagan, Cristina Nostro, Rennian Wang, Lakshmi Muthuswamy, Cheryl Arrowsmith, Sean Cleary, David Schaeffer, Michael Roehrl, Tsao Ming-Sound, Steven Gallinger, Gordon Keller, Senthil Muthuswamy.{Authors}. Ductal cancer modeling using cell patient-derived organoids. [abstract]. In: Proceedings AACR Special Conference on Pancreatic Cancer: Advances Science Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr B45.