Ultra-high sensitive detection and molecular characterization of circulating tumor cells during minimal residual disease in breast cancer

• Applicants: Professorin Dr. Tanja Fehm; Dr. Johannes Fischer; Professor Dr. Christoph Klein; Professor Dr. Nikolas Hendrik Stoecklein
• Subject Area: Gynaecology and Obstetrics
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 533917483

Our research project aims to gain a better understanding of the biology of minimal residual disease (MRD) in breast cancer. MRD refers to disseminated cancer cells that survive in the body of patients after surgery and systemic therapy and are responsible for lethal metastatic relapses. Due to their rarity and technical challenges in analysis, the molecular characteristics of MRD cells and their biology is still largely unknown. Current therapeutic strategies primarily focus on the characteristics of primary tumors rather than the actual target cells - the MRD cells - which can survive for years or even decades before becoming reactivated and giving rise to metastases. Given that circulating tumor cells (CTCs) can be detected in approximately 20% of breast cancer patients in the MRD situation, we propose a project to comprehensively characterize MRD-CTCs in terms of their molecular and functional properties. To achieve this, we will apply our ultra-sensitive leukapheresis approach to isolate CTCs from half of the total blood volume (approximately 2.5 liters) in patients who have been found to have CTCs after completing therapy. Through this clinically safe procedure, we can achieve a high enrichment of MRD-CTCs. This will deliver enough MRD-CTCs to extensively investigate their genomic characteristics and establish their relationship with primary tumors, identify therapeutic targets, and establish and characterize organoids derived from MRD-CTCs. The overarching goal of the project is to develop personalized treatment concepts for breast cancer patients in (neo)adjuvant settings based on a comprehensive understanding of the molecular characteristics and growth ability of MRD-CTCs.

• DFG Programme: Research Grants
• International Connection: Netherlands
• Co-Investigators: Dr. Andreas Brosig; Professor Dr. Olaf Ortmann; Professor Dr. Tilman Rau; Privatdozent Dr. Stephan Seitz
• Cooperation Partner: Dr. Michiel Stevens