Models of high-grade serous carcinoma of tubo-ovarian origin

Biological models aim to recapitulate the molecular and histologic characteristics, as well as the carcinogenesis of the disease of interest, to enable high-fidelity experimentation and impactful translational development. In high-grade serous carcinoma of ovarian, tubal, or peritoneal origin, there is a need to regularly re-evaluate the experimental models being employed to address research questions. This review aims to provide a resource for better understanding the applications, strengths, and limitations of the available models. This work discusses the origin and carcinogenesis of high-grade serous carcinoma and reviews normal cell-of-origin models, as understanding the cellular origin is critical to experimental efforts focused on pathogenesis, disease progression, and prevention. High-grade serous carcinoma cell lines are discussed, including essential and complementary molecular features, cell line management, and limitations. Next, the review examines advances in organoids, with a specific focus on patient-derived organoids from ascites and single-cell suspensions, organ-on-a-chip platforms, and tissue slice technologies. Finally, given the heterogeneity of epithelial ovarian cancer in general, and high-grade serous carcinoma in particular, and the evolving understanding of the importance of the tumor microenvironment, in vivo models capture organism-level complexity. In this review, we focused on high-grade serous carcinoma. In this context, we review patient-derived xenograft (PDX), syngeneic, and genetically engineered mouse models. Each has its own advantages and disadvantages, and guidance is provided on the optimal use of these in vivo approaches for the study of high-grade serous carcinoma.