Ovarian carcinosarcoma (OCS) is the most aggressive histological subtype of ovarian cancer. Its poor prognosis is mainly due to diagnosis at a late, advanced stage and chemotherapy resistant relapses. In this project, we seek to unravel the complex nature of this biphasic cancer consisting of both epithelial/ carcinoma and mesenchymal/sarcoma components. Epithelial-mesenchymal transition is considered the crucial process for the differentiation of epithelial to mesenchymal cancer cells in OCS, but the underlying mechanisms remain elusive. Using unique PDX models and single cell expression analysis, we aim to gain a detailed understanding of the molecular regulators crucial in this carcinoma-sarcoma shift. We suggest that the plastic, hybrid epithelial-mesenchymal cells, bridging the carcinoma and the sarcoma fraction, could be the main determinant of the aggressiveness of this disease. We will specifically focus on these hybrid cancer cells and their presumed role in fuelling chemotherapy resistance in OCS, given the high need for effective ways to prevent this. We will concretely evaluate a putative novel strategy for blocking the malignant behaviour of OCS. Our findings will potentially be extrapolatable to non-gynaecological CS as well. Altogether, this project will provide new insights into the aetiology of this difficult-to-treat cancer and provide interesting and novel directions for a CS-specific, efficient therapeutic strategy.