An effective way to test new drugs in a pre-clinical setting remains a challenging task. Ovarian cancer models are particularly difficult as the tumours are very heterogeneous and although progress has been made with testing cell lines derived from ascites- new platforms are needed. Precision cut tumour slices have been tested for many years and the technique is improving. Organotypic culture could potentially offer an platform to test drugs without having to rely on laboratory animal models. Testing individual tumour' sensitivity to cytotoxics would allow for a personalized approach to cancer treatment and would help to avoid some of the unnecessary toxicity. We have developed an organotypic slice ovarian cancer culture model that allows for testing cytotoxics and targeted agents on tissue taken directly from patients.
Tumour tissue obtained from patients undergoing operation for ovarian cancer was biopsied using a core punch biopsy. The tumours were sliced on a vibrating microtome into 300 µm thick slices and cultivated in culture. Slices were harvested at various time points and fixed in 10% buffered formalin before embedding in paraffin. The viability, morphology, and proliferation index of the cultivated slices were analysed by immunochemistry (IHC) using H&E, ki67, cleaved Caspase 3 assay and compared to the original tumour biopsy. The cultivated tumour slices were also treated with cisplatin and saline control.
Core punch biopsies were obtained from 18 high grade serous ovarian tumors and one endometroid tumour and cultured for up to seven days. The tissue viability assessed using ki67 showed high proliferation rate at the start of the culture and low levels of apoptosis. The apoptosis index varied depending on the individual culture conditions and the number of necrotic cells have increased. The morphology of the tissue was retained throughout. Following administration of cisplatin we were able to observe clear signs of necrotic and apoptotic cell death. The platform is currently being used to test the effect of other cytotoxics as well as novel drugs.
Organotypic slice ovarian cancer model is a new way of assessing sensitivity to anticancer agents and has promising potential for use in personalized cancer treatment
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University of Surrey
All authors have declared no conflicts of interest.