Organoid Models of Human and Mouse Ductal Pancreatic Cancer

Pancreatic cancer is the most lethal malignancy due to its late diagnosis and limited response to treatment. Additionally, pancreatic cancer is predicted to become the second most common cause of cancer death within a decade due to a rising incidence. Therefore, tractable methods that enable the development of new diagnostic and therapeutic approaches for pancreatic cancer patients are urgently needed. Accordingly, we describe the establishment of organoid models prepared from normal and neoplastic adult murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from small amounts of tissue, proliferate indefinitely, cryopreserved, and maintain their ductal and disease-stage specific characteristics. Following orthotopic transplantation, the neoplastic organoids recapitulate the stage of tumor development from which they were derived by forming intraepithelial and cystic neoplasms prior to progressing to invasive carcinomas. Pancreatic organoids provide new molecular and cellular insights into cancer pathogenesis, and enable translational approaches that may improve the care of pancreatic cancer patients.