Clinical translation of a novel microfilter technology Capture, characterization and culture of circulating tumor cells

Abstract

The most important determinant of prognosis and management of cancer is the presence or absence of metastasis [1]. The road to metastasis involves tumor cells to become detached from the primary tumor and travel in the blood to distant sites, causing secondary tumors. These tumor cells traveling in blood are termed Circulating tumor cells (CTC). Capture of CTC from whole blood has been a challenging feat. The fact that these CTC are few in number, to effectively and efficiently isolate them from whole blood can be thought of as looking for a needle in a haystack. Our microfilter technology exploits the use of size based capture of the larger CTC from the smaller white blood cells and components of whole blood. The effective capture potential of the microfilter platform has driven the area of CTC analysis into a new age of research in the field of cancer. The ability to finally analyze CTC at a molecular level, leads to a deeper understanding of metastatic process, while providing an opportunity to evaluate, monitor and manage treatment options as well as the adherent possibility of having an “on-chip” drug sensitivity assay for focused treatment options. We have demonstrated through clinical trials the ability to effectively identify, enumerate and characterize CTC based on immunfluorescence and FISH assays and provide a companion endpoint for monitoring and evaluating treatment management. Our work on viable CTC capture has resulted in successfully capturing and culturing CTC from blood in mouse models that have been inoculated with breast cancer cell lines to form primary and secondary metastatic cancer sites. The future potential within the microfilter technology to capture viable CTC for culture, will catapult therapeutic interventions to a new level of personalized medicine in cancer management.