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 Overall design: 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.