Mouse models of cancers represent an almost obligatory step along the sinuous road toward the design of new drugs for clinical application. There are three distinct uses for such mouse models, the ultimate goal of which, in a combined effort, is to provide new anti-cancer treatments. Mouse models of cancer are particularly well-adapted for understanding the biological principles of cancer (identification of new markers of the disease, putative targets, and the origin of cancer cells), testing anticancer drugs in preclinical studies (neoadjuvant, adjuvant, and anti- metastatic treatments), and assessing the role of environmental conditions (tobacco, diet or environmental stress). The objective of this chapter is to present the diverse mouse models developed to date and, wherever possible, to define what they have taught us about pancreatic tumor-stroma interactions. A thorough overview of mouse models of pancreatic cancers currently available is presented (section I): chemically-induced models, transplanted models, and genetically engineered mouse (GEM) models. Presenting the broad spectrum and variety of mouse models will illustrate the extreme difficulty of selecting the model that is most suitable for answering a precisely delineated question (response to drug, stepwise tumorigenesis, environmental effects, etc.). The knowledge that has been acquired from these mouse models of pancreatic cancers will then be addressed, both at the fundamental and the clinical level (section II.). A particular attention will be paid to how these models have contributed to a better understanding of the cancer cell-stroma interactions. In addition, this chapter will explore how this integrated approach, considering the tumor bulk as a complex multicellular entity, could be used to develop new anti-cancer strategies targeting the complex dialogue between the different cell populations, rather than focusing only on the epithelial cancer cell components.
Copyright © 2012, Transworld Research Network.