ESOPHAGEAL CANCERS AND MODEL SYSTEMS.

Gastrointestinal cancers are largely epithelial in nature and arise from the esophagus, stomach, pancreas, colorectum and liver. In aggregate, these cancers are the most common malignancies in the United States and worldwide, but suffer from poor outcomes in late stages. Our overall work aims to elucidate the following: 1) how normal epithelial cells become metaplastic and dysplastic; 2) how tumor cells invade and interact with activated fibroblasts and immune cells; and 3) how tumor cells disseminate into the circulation and colonize distant organs (metastatic organotropism). We develop three-dimensional cell culture models and genetically engineered mouse models to decipher mechanisms. Our overarching desire is to translate preclinical models to clinical trials that impact upon outcomes in patients with metastatic gastrointestinal cancers. We will frame these principles and approaches in the context of esophageal cancers and three-dimensional models.