Epithelial to Mesenchymal Plasticity and Differential Response to Therapies in Pancreatic Ductal Adenocarcinoma

PDAC epithelial (E) and quasi-mesenchymal (QM) subtypes can be modulated by different therapies demonstrating the plasticity of PDAC cells that contributes to the heterogeneity of PDAC tumors and their intrinsic resistance to a broad spectrum of therapies. Understanding and monitoring the fluidity of PDAC E and QM states are critical to the development of improved clinical trial design to target these different subpopulations PDAC cell lines were grown in 3D culture and treated with chemotherapeutic agents (FOLFIRINOX), Vitamin D (calcitriol) or the appropriate vehicle controls. Tumorspheres were harvested at varying timepoints following treatment for RNA purification, library preparation and next generation sequencing. For some samples including Vit D treatment of PDAC cell lines, experiments were performed in duplicate or triplicate as indicated.