Senior Collaborator/Clinical Advisor

Background: The progress in basic ovarian cancer research has been slow, mainly because of the lack of appropriate animal models that develop epithelial ovarian carcinomas (EOC). Recently, two approaches have been reported that successfully induced EOC in vivo 1,2. One is based on the avian retroviral receptor TVA-replication-competent avian leucosis virus-derived vector (TVA-RCAS) gene delivery technique for introduction of defined alterations in explanted ovarian surface epithelium. In this system, the TVA receptor can be restricted to the surface epithelial cells by use of the cytokeratin (CK) 5 promoter 1. The second uses the Mullerian inhibitory substance type II receptor (MISIIR) regulatory element for the specific expression of the SV40 T antigen in the ovarian surface epithelium 2. The advantage of the MISIIR promoter system is that it is able to model complete development of disease from intact normal ovary. However, like most transgenic mouse models, the MISIIR system also carries germline genetic modifications during embryonic development, while the majority of human cancers arise in somatic cells, initiating neoplasia in the adult. Therefore, only the TVA-RCAS system can circumvent these problems and also provide the opportunity to rapidly test oncogenes and tumor suppressors both singly and in combination in vivo 3