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Abstract High-grade serous ovarian carcinoma (HGSOC) is the most common form of ovarian cancer (OC). This heterogeneous disease is associated with various molecular alterations influencing the disease course. Unfortunately, the impact of those molecular alterations on the response to therapy is still misunderstood. Few OC models allow control of genetic background in the cancer cells while preserving the tumor's architecture and microenvironment, including the immune cells. Furthermore, there is currently no high-throughput model that retains those characteristics and is suitable for drug screens. This project aims to develop a high-throughput syngeneic murine organotypic tumor slice culture model to study the impact of common HGSOC molecular alterations on anticancer drug responses. The pre-established Trp53−/− syngeneic OC mouse model has been genetically engineered to represent molecular alterations frequently found in HGSC. Ten variants were produced by overexpressing Tp53R172h and overexpressing oncogenes such as Ccne, Brd4, Myc, Ndrg1, and Pik3ca and/or deleting Brca1, Pten, and Nf1. After validation and characterization of the cells in vitro, we performed allografts in immunocompetent C57/bl6 mice and obtained tumors with HGSOC histology. The tumors were used to develop an organotypic tumor slice culture model. Briefly, each tumor is collected and thinly sliced with a vibratome. Each slice can be cultured for several days without significant cell death induction and can be used for a drug screen. Our preliminary data shows that the model preserves the HGSOC histology over six days and remains viable. A viability assay has also been developed to assess the sensitivity of the tumor slices to various anticancer drugs. In conclusion, this project will allow the development of a platform for screening anticancer therapies against HGSOC and will lead to a better understanding of the relationship between HGSOC's common molecular alterations and the responses to therapy. Citation Format: Violaine Pourcel, Emile Létourneau, Dominique Jean, Marilyne Labrie. A novel ovarian cancer organotypic tumor slice culture model abstract. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84 (5 Suppl₂): Abstract nr A101.
Pourcel et al. (Mon,) studied this question.