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Although primary treatment is often effective, the prognosis for patients with metastatic cancer is poor as they experience increasingly therapy-resistant relapses. To improve the prognosis, it is important to be able to eliminate all metastases that can sustain the development of cancer through genetic and phenotypic changes that make them therapeutic. We will use tumor and stromal cells from patients with aggressive metastatic ovarian cancer. We will investigate how cancer cells avoid cell death and how tumor microenvironment-induced phenotypic plasticity confers therapy resistance. We will establish ex vivo 3D co-cultures, tissue models and so-called live cell imaging to investigate therapy resistance. The project aims to reveal important molecules and signaling pathways that make cancer cells invasive and resistant to therapy. The goal is to identify biomarkers and signaling pathways for which we can provide targeted therapy in later translational studies and which can help improve the prognosis of patients with advanced ovarian cancer and other equally aggressive cancers.