Abstract 192: Ex vivo screening and analysis of novel effective treatments for ovarian cancer

Abstract

Abstract Purpose: Ovarian cancer is the most lethal gynecological cancer. Histologically, about 90% of the ovarian cancers have epithelial origin and more than 75% are characterized as high-grade serous ovarian cancer (HGSOC). Despite having a good primary response to the standard platinum-taxane based chemotherapy, almost all HGSOC patients experience a relapsed disease. The 5-year survival rate of ovarian cancer is only 38% globally, indicating need for the development of novel efficient treatments to fight the resistance. Here we have established a personalized drug screening and evaluation platform using HGSOC patient samples and medicines approved for treatment of different types of cancers. Methods: Tissues collected from ovarian cancer patients were grown as 3-dimensional (3D) ex vivo long-term tumor organoid cultures. Seven HGSOC cell lines were additionally grown as spheroids or as xenograft tumors to establish them as 3D tumor organoid cultures for drug efficiency evaluation. Cancer stemness and further classification of samples were determined via immunofluorescent staining with relevant antibodies (pax8, Ki67, acetylated tubulin, p53, cytokeratin-8) and consequent high-throughput imaging using the ImageXpress Micro Confocal microscope (Molecular Devices). The images were analyzed and quantified using MetaXpress software. Organoid growth and response to tested treatments was validated via invasive growth and survival assays. Both assays were used to monitor resistance of organoids towards cisplatin and carboplatin treatment and towards suggested potential new treatments. Cancer drugs were selected according to suggestions based on RNA seq, DNA and/or drug screenings done in cancer cell lines. A preclinical mouse model (in immunodeficient NOD/Shi-scid/IL-2Rγnull (NOG) mice) was set up to be used for in vivo validation by monitoring the tumor growth in response to the treatment. Results: Currently, 20 patient tumor samples received from Turku University Hospital, Finland (KH, JH) have been cultured in 4 different culture media to obtain highest possible survival rates for each sample. Organoids from ovarian cancer cell lines are characterized for their resistance to increasing concentrations of platinum treatment. Notably, organoid analysis protocols and screening conditions have been setup for the high-throughput microscopy. These include organoid growth, survival, and invasiveness/aggressiveness. We are currently set up for screening organoids with the first drugs suggested by bioinformatics-based genetic pathway analysis and drug screening studies in cancer cell lines. The results of the screen will be presented. This study is a part of a large EU-funded ovarian cancer project DECIDER (https://www.deciderproject.eu/). Citation Format: Aikaterini Skorda, Kaisa Huhtinen, Wojciech Senkowski, Krister Wennerberg, Sampsa Hautaniemi, Johanna Hynninen, Tuula Kallunki. Ex vivo screening and analysis of novel effective treatments for ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 192.