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New model systems to advance understanding of serous epithelial ovarian cancer

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Improving outcomes for women with epithelial ovarian cancer (EOC) is a major health issue worldwide. However, despite advances in surgical techniques and chemotherapy, the 5-year survival for women with EOC has not improved significantly over the last two decades. It is now recognized that EOC is not a single ...

Improving outcomes for women with epithelial ovarian cancer (EOC) is a major health issue worldwide. However, despite advances in surgical techniques and chemotherapy, the 5-year survival for women with EOC has not improved significantly over the last two decades. It is now recognized that EOC is not a single entity but rather a number of distinct malignancies with different etiologies and molecular aberrations. Of these, high grade serous EOC (SEOC) is the most aggressive and common, accounting for 60-70% of all cases of ovarian cancer. The urgent need to increase our understanding of this malignancy led to it being chosen for the pilot project of The Cancer Genome Atlas and the genomes of over 400 SEOC 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.

Notwithstanding this unprecedented in silico resource, research in SEOC 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 SEOC has its origins in the secretory cells located in the fimbrial end of the fallopian tube. This is contrary to the prevailing notion that SEOC arises from the epithelium lining the ovary and inclusion cysts. The contribution of each site to serous ovarian carcinogenesis is currently under debate. Understanding disease development requires models of tumor progression and is best addressed by spontaneous mouse models. However there is a paucity of reproducible spontaneous animal models of this disease. This may be partly explained by the lack of promoters to drive genetic changes in the cell of origin of this disease. However, circumventing this technical difficulty by surgical delivery of Cre recombinase has not always delivered the expected outcomes. Does this again relate to the cell of origin?

New models for the study of SEOC are being generated to accommodate the changing view of the cell of origin and enable monitoring of tumor progression. These will facilitate timely and full exploitation of the exceptional in silico resources now available to ultimately improve outcomes for women affected by this malignancy. This Frontiers research topic will showcase new model systems for SEOC research including normal, cancerous and cancer-associated cell lines and their use in 2D, 3D and co-culture systems as well as in vivo approaches that utilize the latest advances in transgenics and imaging. It will include method articles for the establishment of new models and research papers detailing the insights gained from the use of these new models. In addition, new hypotheses related to the success and failure of current and proposed models are encouraged as well mini-reviews and perspectives of established systems.

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