The role of the tumor microenvironment in pancreatic ductal adenocarcinoma and preclinical models to study it

Pancreatic ductal adenocarcinoma (PDAC) is a very lethal disease, mostly due to late diagnosis, aggressive growth, and therapy resistance. The tumor microenvironment (TME) of PDAC is one of the main hallmarks to contribute to therapy resistance and has been intensively studied over the years. Despite these efforts, a strong discrepancy exists in the translation of preclinical studies to clinic, which is partly due to the lack of models that accurately reflect human PDAC. This chapter gives an overview of the role of the TME in PDAC. In addition, the most important applications and (dis)advantages of traditional (e.g., monolayer cell lines, cell line-based and patient-derived xenograft mouse models) and novel (e.g., three-dimensional culture systems, organoid-based mouse models) preclinical models for PDAC are described.