Cancer Research in Rat Models

Rat has been the major model species used in several biomedical fields, notably in drug development and toxicology, including carcinogenicity testing. Rat is also a useful model in basic cancer research. Several rat models of monogenic (Mendelian) human hereditary cancers are available. Some were obtained spontaneously, while others were generated either by mutagenesis of tumor suppressor genes or by transgenesis of activated oncogenes (transgenesis can be performed efficiently in the rat). In addition, among the hundreds of inbred rat strains that have been isolated, some are highly susceptible or resistant to certain types of cancer, and these divergent phenotypes were shown to be polygenic. Numerous quantitative trait loci (QTLs) controlling cancer susceptibility/resistance have been defined in linkage analyses, and several of these QTLs were physically demonstrated in congenic strains. These studies led, in particular, to rapid translation to the human, with the identification of loci controlling susceptibility to a form of multiple endocrine neoplasia (monogenic trait) and to breast cancer (polygenic disease). The biology of cancer resistance has also been analyzed, and in some (but not all) cases, it was linked to regression of preneoplasic lesions. Rat tumors have been the subject of various types of analyses, and these studies led to important conclusions, including that tumors can be classified on the basis of the identity of the inducing agent, thereby suggesting that analyses of human tumors may be valuable in determining retrospectively the role of specific carcinogens in the formation of human cancers, and of human breast cancer in particular.