The laboratory mouse has been a central player in cancer research for the better part of this century. Particularly over the past two decades, numerous laboratories have used the techniques of transgenesis and gene targeting to create novel mouse strains to study cancer. The analysis of these strains has led to an improved understanding of the genes involved in tumorigenesis in humans, the histopathological progression of cancer, and many other aspects of the disease process that can only be studied in the context of the whole animal. With more genes, more powerful methods of genetic manipulation and greater insight into tumor profiles on the molecular and cellular levels, the long-standing goal to create genetically and histopathologically accurate models of cancer development in the mouse is beginning to be realized. This special issue of Oncogene features reviews by many leaders of the effort to model human cancer in the mouse, and collectively they provide a view of the ‘state of the art’ in this burgeoning field.
Historically, transgenic strains carrying activated forms of oncogenes or conventional ‘knockouts’ of tumor suppressor genes have been generated to test the causal relationship between the expression (or lack of expression) of a gene and tumor development. These ‘first generation’ models initially validated the importance of particular genes and their mutations in tumorigenesis. Additional efforts with these models have included the combining of multiple cancer-associated mutations in a single animal, the discovery of cooperating mutations using insertional mutagenesis, and the initial molecular genetic analysis of tumor maintenance and progression. As a better understanding of cancer-associated pathways has emerged from these and other studies, more directed experiments in the mouse have been undertaken, which have sometimes confirmed or otherwise challenged the importance of a given gene or process in tumor development.
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