Mouse models for actinic keratosis and squamous cell carcinoma

This manuscript focuses on the use of mice to study the genetics and biology of cutaneous squamous cell carcinoma (SCC). Mice develop actinic keratosis-like lesions and SCC resembling those seen in humans. As an animal model, the mouse provides great experimental flexibility and has been useful in investigating aspects of the genetics and biology of SCC that are difficult to study in humans. We discuss the pros and cons of the various murine models available. How well mouse pathology in general mimics human disease remains an open question due to the vast differences in animal strain backgrounds and the fact that only one strain is typically tested in any particular experiment. Nonetheless, the murine epidermis is thinner than the human epidermis, and this must be kept in mind when making inferences from mechanistic data obtained with mice. We outline new strategies for non-biased screens to discover genes driving SCC progression. Such work has revealed a very complex interactive molecular network, and as with other complex diseases, the picture is being pieced together using systems biology strategies to which mouse tumour models are amenable. Such approaches do not focus on single genes or proteins but try to integrate the complex interactions of many types of genetic and biological information.