Diagnosis in an advanced state is a major hallmark of ovarian cancer and recurrence after first line treatment is common. With upcoming novel therapies, tumor markers that support patient stratification are urgently needed to prevent ineffective therapy. Therefore, the transcription factor FOXM1 is a promising target in ovarian cancer as it is frequently overexpressed and associated with poor prognosis. In this study, fresh tissue specimens of 10 ovarian cancers were collected to investigate tissue cultures in their ability to predict individual treatment susceptibility and to identify the benefit of FOXM1 inhibition. FOXM1 inhibition was induced by thiostrepton (3 µM). Carboplatin (0.2, 2 and 20 µM) and olaparib (10 µM) were applied and tumor susceptibility was analyzed by tumor cell proliferation and apoptosis in immunofluorescence microscopy. Resistance mechanisms were investigated by determining the gene expression of FOXM1 and its targets BRCA1/2 and RAD51. Ovarian cancer tissue was successfully maintained for up to 14 days ex vivo, preserving morphological characteristics of the native specimen. Thiostrepton downregulated FOXM1 expression in tissue culture. Individual responses were observed after combined treatment with carboplatin or olaparib. Thus, we successfully implemented a complex tissue culture model to ovarian cancer and showed potential benefit of combined FOXM1 inhibition.
e18090 Background: The standard therapy of patients with ovarian cancer consists of primary surgery followed by chemotherapy. Initial response rates are very high, but recurrence occurs in 85% of the cases. Personalized ex vivo analyses of various anti-tumor compounds in a standardized tissue slice culture system (1) might be a very promising approach for individualized therapeutic decisions. In comparison to cell culture, tumor slice cultures maintain the direct tumor microenvironment which plays a role in resistance mechanisms and thus therapy response. Methods: Patient derived tumor cultures (1) are grown under standardized conditions and are analyzed semi-automated. Patient’s tumor samples were collected during surgery, cut into standardized slices and were cultivated in triplicates for 2, 4, 7 and 14 days and treated with standard therapy for 7 days. A baseline control was prepared at day 0. The cultured tissue is PFA-fixated and paraffin embedded. Hematoxylin eosin staining was performed for microscopic evaluation of morphologic structures. Subsequently, immunohistochemical staining against CD3 was applied to examine the immune setting of the tumor and its environment. Results: Ovarian tumor tissues remained their morphological properties over a period of 14 days. Parameters like cellular formation, proliferation and heterogeneity were adequately represented in the cultures.. Staining against CD3 revealed T-cells in ovarian tumor tissue slices up to 14 days ex vivo and individual response to treatment was observable. Conclusions: Correlation to clinical data is ongoing to analyze the tissue culture model of ovarian cancer for clinical usage. Different approaches, concerning mutational burden, immunological signature and histology are considered for decision of response and non-response.
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