The role of Neural Proteins in the Development of Epithelial Ovarian Cancer

• Applicant: Dr. Charlotte Sachs
• Subject Area: Gynaecology and Obstetrics ; Hematology, Oncology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 585996725

Low-grade serous ovarian carcinoma (LGSOC) is a rare but clinically particularly challenging subtype of epithelial ovarian cancer. It frequently affects younger patients, is characterized by pronounced resistance to chemotherapy, and typically follows a chronic disease course with repeated recurrences. LGSOC commonly arises from serous borderline tumors (SBTs), which are considered non-invasive precursor lesions. The biological mechanisms that govern the transition from these early, non-invasive precursor lesions to invasive carcinoma remain insufficiently understood and represent a major gap in knowledge in ovarian cancer research. The aim of the proposed project is to identify and functionally characterize novel molecular programs that contribute to malignant progression from serous borderline tumors to low-grade serous ovarian carcinoma. Building on recent preliminary work, the project will investigate to what extent neuronal proteins are aberrantly activated during this progression process and whether their activation promotes invasive and metastatic properties of tumor cells. Initial data suggest that proteins originally described in the context of neuronal development and function are selectively reactivated during ovarian tumor progression. A central focus of the project is the neuronal RNA splicing factor NOVA2, which is exclusively expressed in LGSOC but not in SBTs and promotes tumor growth, cell migration, and invasiveness in experimental models. The objective is to identify the molecular networks regulated by NOVA2 and to systematically investigate their functional relevance for tumor progression. To achieve this, human tumor tissues as well as established cell, tissue, and animal models will be employed, in which the activity of neuronal proteins will be specifically modulated. This approach will allow assessment of their effects on tumor growth, invasion, interactions with the tumor stroma, and metastatic dissemination. In the long term, the project aims to obtain an in-depth mechanistic understanding of LGSOC progression. The resulting insights are expected to provide the basis for the identification of novel biomarkers for risk stratification and for the development of innovative, targeted therapeutic strategies, thereby contributing to improved clinical management of affected patients.

• DFG Programme: Fellowship
• International Connection: USA
• Host: Professor Dr. Ernst Lengyel