Kras in Organoids

Oncogenic Kras are genetic dependencies for the majority of pancreatic and colorectal adenocarcinomas; however, much remains to be understood regarding its tropism to these carcinomas. Recently developed organoid technology presents a more representative model culture system for pancreatic and colon epithelial tissues as well as better fostering the culture of nonimmortalized cells than two-dimensional culture. These advantages enable cancer researchers to directly compare tumor and normal tissue models to better study tumor initiation as well as therapeutic efficacy. Although in vivo models better model the complexity of multiple cell types, the organoid system allows for easier genetic manipulations and isolation of specific cell types. Furthermore, syngeneic orthotopically transplanted organoids recapitulate tumor histologically and gene expression of the tumors from which they were derived. Thus, organoids may extend the use of genetically engineered mouse models. These advantages of organoid cultures allow for many questions, including but not limited to studying the interaction between different cell types within a tumor and elucidating dependencies of Kras-driven tumors.