Editorial: Advances in Epithelial Ovarian Cancer: Model Systems, Microenvironmental Influences, Therapy, and Origins

Improving outcomes for women with epithelial ovarian cancer is a major health issue worldwide as 5-year survival has not improved significantly over the last two decades. The urgent need to increase our understanding of high-grade serous ovarian cancer (HG-SOC) led to it being chosen for the pilot project of The Cancer Genome Atlas (TCGA) and the genomes of over 400 HG-SOC samples are now freely accessible for interrogation. These data are being used for the discovery of biomarkers as well as the generation of hypotheses to understand the natural history of this malignancy and develop effective targeted therapies. In this Research Topic, Lisowaska and colleagues used gene expression profiling to identify that reduced expression of CLASP1, a regulator of microtubule dynamics essential for mitotic cell cycling was positively associated with survival, either overall or disease free (1). Their data clearly highlighted that different histological subtypes of ovarian cancer had very different molecular signatures, although undifferentiated and high-grade serous ones were indistinguishable. These results are consistent with other findings that together have led to the understanding that epithelial ovarian cancer (EOC) is not a single entity but rather a number of distinct malignancies with different etiologies and molecular aberrations. Of these, HG-SOC is the most aggressive and common, accounting for 60–70% of all cases of ovarian cancer. Notwithstanding the unprecedented in silico resource now available via TCGA and other webbased portals, research in HG-SOC is hampered on a number of fronts. Comparison of results from cancerous or cancer-associated stromal cells with each non-cancerous (normal) equivalent is a fundamental research question, but what to use for normal cells is unclear. Recent evidence suggests that HG-SOC has its origins in the secretory cells located in the fimbrial end of the fallopian tube. This is contrary to the prevailing notion that HG-SOC arises from the epithelium lining the ovary and inclusion cysts. The contribution of each site to serous ovarian carcinogenesis is currently under debate. Jones andDrapkin recount the evolution of evidence for each site of origin and review the use and limitations of primary cell culture model systems developed from each site (2). In support of an ovarian surface epithelial (OSE) origin for HG-SOC,McCloskey and colleagues describe the tumorinitiating characteristics of a novel spontaneously transformed mouse OSE cell line (3). Ahmed and Stenvers draw attention to ascites, an underutilized yet readily accessible source of primary cancer cells from EOC patients and provide a detailed review of its use as a clinically relevant model system (4).Differentmethods of isolation and culture of primary ovarian cancer tumor cells fromascites and other sources are reviewed by Cunnea and Stronach who also advocate for universal standardized protocols for improved reproducibility and interpretation of results between studies (5). In conjunction with the development of new cell models is the move to three-dimensional (3D) culture conditions. 3D culture systems feature in several articles in this Research Topic indicating the enthusiasm for this culture type and recognition of the deficiencies of themonolayer systems (2, 5, 6).