Disease Heterogeneity and Immune Biomarkers in Preclinical Mouse Models of Ovarian Carcinogenesis

Abstract : Ovarian epithelial tumors are highly diverse and the exact tissue of origin is still unclear. Until recently, all five histological subtypes of ovarian epithelial tumors (serous, endometrioid, mucinous, clear cell and transitional adenocarcinomas) were believed to arise in the coelomic epithelium that covers the ovarian surface epithelium (OSE) which then undergoes metaplasia and changes to m llerian -like epithelium before malignant transformation. More recently, however, it has been suggested that they could instead arise directly from extraovarian tissues that are embryologically derived from the m llerian ducts. Although scientific evidence in support of both theories exists, further studies on disease pathogenesis are needed. Our studies use previously described, genetically engineered mice (Cre-loxP) that carry the lox-Stop-loxPKrasG12D oncoallele and a floxed region within region encoding for the phosphatase domain of the Pten gene (KrasPten mice1). We postulate that similarly to intrabursal injections, AdCre injection along various other sites of the genital tract of KrasPten and of our recently described MUC1KrasPten mice 2 will allow us to study in vivo tumor initiation and progression and to identify important disease pathogenesis mechanisms in ovarian tumors and other cancers of the genital tract. Furthermore, in conjunction with our clinical studies we aim to identify novel disease biomarkers that may help in the early diagnostic of ovarian cancer and provide new therapeutic/preventive targets.