Genetically Engineered Mouse Models for Studying Radiation Biology and Radiosensitizers

Genetically engineered mouse models (GEMMs) are powerful research tools that have improved our understanding of cancer and enabled the identification of novel targets for the radiosensitization of human cancer. The use of GEMMs in cancer has evolved significantly since early models of organism-wide oncogene knock-in and tumor suppressor knock-out mice. Advances in recombinase technology have enabled the development of GEMMs with site- and tissue-specific genetic manipulation and temporal control of multiple genetic alterations. There are multiple advantages to using GEMMs to study radiation biology when compared to in vitro or transplant in vivo models. First, they provide a robust platform for the study of normal tissue injury generated by treatment with radiation therapy and radiosensitizers. Second, tumors develop in a native microenvironment, which preserves the stromal and vascular compartments. Third, they allow precise spatial and temporal control of multiple genetic alterations, allowing scientists to dissect the effect of specific genetic mutations on tumor development and radiation response. Finally, these mice have an intact immune system that co-evolves with tumor formation, which is critical to evaluating combined radiation therapy and immunotherapy. Here we review current approaches to mouse modeling for the study of radiation biology and radiosensitizers.