Precious GEMMs: emergence of faithful models for ovarian cancer research.

The development of Genetically Engineered Mouse Models (GEMMs) has catalyzed tremendous progress in cancer research. However, it has been difficult to design adequate mouse models for high-grade serous carcinoma (HGSC), the most common and lethal form of ovarian cancer. The genetic complexity of the disease, as well as the recent appreciation that most HGSCs arise from the fallopian tube (FT) secretory epithelium rather than the ovarian surface epithelium, has stifled the development of robust GEMMs. In a recent issue of this journal, Zhai et al presented an elegant mouse model for ovarian cancer that uses Ovgp1 as an FT-specific promoter to inactivate Brca1, Trp53, Rb1, Nf1, and Pten. The authors showed that loss of these genes in the mouse FT epithelium can mimic the different stages of human HGSC tumorigenesis. Their robust model emphasizes the importance of considering both the cell of origin and tumor genetics in developing accurate model systems. They provide a useful tool for studying mechanisms of disease in vivo and for research into novel methods of prevention, early detection, and treatment of HGSC.