BASIC DATA OF THE RESEARCH PROJECT

• ARRS code: J3-60068

• TITLE: Circulating tumor cell translational research platform
• PRICE CLASS: C
• PROJECT LEADER: Tanja Jesenko, PhD, Prof.
• DURATION: 1.1.2025 – 31.12.2027
• FINANCING: Slovenian Research and Innovation Agency

SHORT SUMMARY:

Circulating tumor cells (CTC) have emerged as an important biomarker in breast cancer, offering indispensable insights into disease progression and therapeutic response. Representing an intermediate stage in the metastatic cascade, monitoring CTC levels in the bloodstream holds profound implications for patient management. The isolation of CTCs from the complex environment of blood components is a major challenge due to their low abundance. However, various state-of-the-art techniques, such as microfluidic devices, immunomagnetic separation, and size-based filtration, have been developed to capture and isolate these cells. These methods enable the enrichment of CTCs from a blood sample and facilitate subsequent analysis. The isolation and study of CTCs is becoming an essential research interest of any comprehensive cancer center. In our institution, the first steps were taken in 2020. We were looking for a simple method for CTC isolation and detection that would allow the classical evaluation of cells by a cytopathologist, which is still a golden standard in cancer diagnostics. We evaluated two methods for CTC isolation in breast cancer patients. The physical method Parsortix  proved to be superior as it allowed the isolation of higher yields of CTCs and the isolated cells were morphologically preserved, allowing their identification and characterization by a cytopathological examination. After these first valuable experiences and the establishment of an interdisciplinary team of researchers, clinicians and cytopathologists, the next step is to set up a translational research platform that will be available for the study of CTCs in different types of cancer. The objective of the proposed project is therefore to establish a translational platform for CTC research at the Institute of Oncology Ljubljana, which is the leading comprehensive cancer center in Slovenia. In establishing the platform, we will focus on breast cancer based on our experience with breast cancer CTCs. In WP1, the in vivo platform will be established, which will enable the study of CTCs in mice. The in vivo platform will enable the evaluation of new treatment strategies and basic research of metastatic process and CTC biology. Furthermore, the fast access to CTCs in preclinical environment will enable us to test different culturing conditions to set up a culturing protocol for CTCs. The second objective will therefore be to establish a platform for the ex vivo culturing and expansion of CTCs in WP2. The established platforms will then be validated by practical case studies, currently of interest in our institution. The first (WP3) will be the evaluation of CTCs after electrochemotherapy. We will validate the in vivo platform to enumerate and characterize CTCs after electrochemotherapy in order to evaluate another safety and efficacy aspect of the treatment. In the second practical case study (WP4), we will validate the ex vivo cultivation platform in isolated CTCs from breast cancer patients.