Ovarian cancer can be effectively treated if caught early, but it is generally diagnosed after it has metastasized. This has a serious impact on the survival of patients, and has also limited our knowledge of the early genetic changes that induce ovarian cancer. Sandra Orsulic et al., reporting in the launch issue of Cancer Cell, have developed the first mouse model of ovarian cancer with defined genetic lesions, which should improve our understanding of cancer development.

Trp53 +/+ and Trp53−/− ovarian cells from transgenic mice that express an avian virus receptor were transfected in vitro with avian retroviral vectors carrying oncogenes that are frequently amplified or mutated in human ovarian cancer: Kras2 , c- Myc and Akt . The authors investigated which combinations of genetic lesions could induce tumour formation in vivo by injecting these ovarian cells subcutaneously into nude mice and monitoring for tumour growth. Tumours arose only from cells that were deficient for Trp53, and had acquired at least two oncogenes by infection.

But can these cells also induce tumour growth at their natural site of formation: the ovaries? Implantation of infected cells under the ovarian capsule of nude mice results in ovarian tumours within 2 weeks. These metastasize to the same sites as human ovarian cancers within 4 weeks.

As the immune system might limit tumour growth in humans, the infected ovarian cells were also implanted under the ovarian capsule of the immunocompetent mice from which the cells were removed; ovarian tumours developed after three months.

This mouse model should help unravel the molecular basis of ovarian cancer development, and will provide a system for testing new therapeutic approaches.