CTCclinUT - clinical utility of CTCs in metastasized breast cancer patients enabled by diagnostic leukapheresis

• Applicant: Professor Hans Neubauer, Ph.D.
• Subject Area: Gynaecology and Obstetrics
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 439913073

Over the last decades targeted therapy has become the preferred approach to treat breast cancer (BC). However, the predictive utility of the primary tumor to select a therapy is limited and obtaining serial biopsies of metastatic lesions is challenging. Thus, in order to manage BC the idea of deriving information on its molecular Achilles heel from liquid biopsies by analyzing e.g. circulating tumor cells (CTCs) is very intriguing. CTCs are shed into the blood by tumor tissue and are commonly considered as precursor cells for metastasis formation. The CTC count is a strong prognostic factor, which can be used to monitor treatment efficacy, but CTCs have not been implemented into clinical practice due to missing proof of their clinical utility to predict individualized, specific and successful treatment strategies. The main cause for this dilemma is the rarity of CTCs detected and isolated from blood, which is preventing both comparative basic analytic and pre-analytic CTC-research in order to uncover the different biology of CTCs. This, however, is absolutely needed in order to develop future individualized and CTC-based therapy decision. With the project presented here - CTCclinUt - we plan to overcome these challenges by performing longitudinal CTC-analyses of metastasized BC index patients who suffer from high CTC-numbers and who have undergone additional diagnostic leukapheresis (DLA) – a method pioneered in Duesseldorf to isolate tumor cells from a patient’s total blood volume. In combination with latest technologies for parallel high throughput molecular analyses this will enable us to investigate complex CTC populations for genomic mutations, gene copy number variations, and gene expression profiles on single cell level. In this way CTCclinUt will give us insights into the CTCs’ heterogeneous biology and their clonal evolution during disease and therapeutic intervention and will help us to understand resistance mechanisms activated during treatment history. The final aim will be to translate the CTCs’ molecular characteristics into optimized therapy regimen.

• DFG Programme: Research Grants
• Co-Investigator: Professorin Dr. Tanja Fehm