Development of Optimized Ex Vivo Organotypic Slice Culture Systems
The main goal of this project is to develop an efficient and robust ex vivo tumor slice cultures to bridge the gap between in vitro cell culture studies and in vivo animal model studies. The current mainstream pipeline for drug discovery heavily relies on initial studies in established human cancer cell lines; however, these cell lines lack the cellular complexity present in most malignant tumors and have diverged from the original tumor at the molecular level; hence, no longer modeling the original disease in the patient.
While in vivo animal models provide the organismal complexity for the most part, animal studies are less amenable to experimental manipulations, very costly, and time consuming. In contrast, organotypic slice cultures (live tissues cut to thin slices) are amenable to genetic, chemical and physiological manipulations that can be monitored in real time, over long periods of time, and in longitudinal studies. Furthermore, they can provide relatively cost effective and rapid experimental paradigms. In addition, they provide platforms to study native cellular interactions between cancer cells and their microenvironment. By combining genetic tools that are available, such as mouse strains that have unique populations of cells labeled with different fluorescent molecules, tumor slice cultures can advance our understanding of cancer biology to a new level, improve drug development pipelines, and even inform smarter therapy combinations. Therefore, we propose to develop, optimize, and validate tumor slice cultures from brain, breast, colon and pancreatic cancers in this study.