Multistage Carcinogenesis: Cell and Animal Models

Carcinogenesis is a multistage process that involves numerous etiologies that work at different stages of tumor development. Our ability to dissect oncogenic events is largely dependent on the availability of model systems that recapitulate human carcinogenesis at both the pathological and molecular levels. With progress in molecular and cell biology, studies with cell model systems have produced many important conceptual advances for our understanding of the mechanism of carcinogenesis. In parallel, animal models provide the tissue and the systemic contexts of carcinogenesis and serve to validate molecular predictions and targeting opportunities in cancer prevention and treatment. With the development of genetically engineered mouse models, the functional consequences and tissue dynamics of genetic alterations can be defined at discrete stages of carcinogenesis. The cooperative models that bridge cell culture techniques and corresponding animal models offer simple and quantitative approaches to evaluate the oncogenic potential of carcinogens (chemical, viral, and physical agents), immunity, as well as the roles of discrete candidate cancer genes in carcinogenesis. The choice of a model is of importance and should consider the cell/tissue type of origin, the molecular and microenvironmental complexity of carcinogenesis, the variety of carcinogen and therapeutic reagents to be tested, and the relevance to human cancer.