Multistage Carcinogenesis: Cell and Animal Models

Carcinogenesis is a multistage process that involves numerous etiologies that work at different stages. Our ability to dissect oncogenic events is largely dependent on the availability of model systems that recapitulate human carcinogenesis at pathological and molecular levels. With the 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 are required to provide the tissue and the systemic contexts of carcinogenesis and to validate molecular predictions and targeting opportunities in cancer prevention and treatment. With the development of genetically engineered mouse models, it is possible to define the function and dynamics of genetic alterations at discrete steps in carcinogenesis. The cooperative models that bridge cell culture and corresponding animal sites offer simple and quantitative approaches to evaluate the oncogenic potential of carcinogens (chemical, viral, and physical agents) as well as the roles of discrete candidate cancer genes in carcinogenesis. The choice of a model is of importance and should take into account the cell/tissue type of origin, the complexity of carcinogenesis, the variety of carcinogen and therapeutic reagents to be tested, and the relevance to human cancer.