Main Host Institution: Institution: University Medical Center Hamburg – Eppendorf, Department of Tumor Biology (UKE) – Germany

Host Lab: Cell stress and dissemination

Project Title: Detection and characterization of CTCs in NSCLC

Project Background: The discovery of CTCs is considered as a breakthrough in translational research. In fact, the current knowledge of cancer evolution suggests that growing cancer continuously shed CTCs into the bloodstream upon invasion with the striking ability to colonize second sites and form metastatic foci. Detection of these disseminated tumor cells within the bloodstream is thus of a primary importance in light of its ability to provide valuable information about the disease. The CellSearch system is the only FDA approved tool for CTC detection in breast, prostate and colorectal cancer. It is based on epithelial marker expression (EpCAM, cytokeratin), and therefore its proper use in NSCLC in still being debated because of its low sensitivity. This issue is mainly due to high diversity of CTCs phenotypes in NSCLC and high proportion of cells that have potentially undergone epithelial-to-mesenchymal transition (EMT). Therefore, further understanding of the molecular switch bases underlying these disseminated cells upon invasion seems plausible along with further cellular characterization of the targeted tissue forming cancer. The only use of CTCs might not be sufficient to overcome all the challenges inherent to early screening and monitoring. Only an integrative approach of more than one liquid biopsy based biomarkers will allow for a serious approach to the benefit of early stage cancer screening, prognosis appreciation and prediction of treatment response. In order to guide NSCLC therapy and screen for early diagnosis of progression and resistance to targeted therapy, peripheral blood might present an alternative source for tumor enriched material. By using several liquid biopsy based biomarkers and besides the sub-mentioned aims above, one of the specific aims is to identify and characterize different subpopulations of CTCs including EMT/stem cell like CTCs which could allow for development of new therapeutic strategies for a subgroups of NSCLC patients with limited therapeutic options.

Project Aim:

• Develop a multicolour staining cocktail for the detection of different subpopulations of CTCs (biological properties) and develop the microarray chip for the same aim (physical properties).
• Isolation, detection and molecular characterization of blood-based biomarkers in NSCLC patients.
• Computational approach for big data analysis combined with our own NGS data (will be performed in Granada and Sofia within the EU-funded ELBA consortium).
• Validation of data for an integrative approach capable of combining the 4 blood-based biomarkers to propose a serious strategy for NSCLC diagnosis of progression and resistance to targeted therapy and a potential early screening disease methodology.