Functional analysis of circulating tumour cells: the KEY to understand the biology of the metastatic cascade

Abstract Metastasis formation is the main cause of cancer-related death in patients with solid tumours. At the beginning of this process, cancer cells escape from the primary tumour to the blood circulation where they become circulating tumour cells (CTCs). Only a small subgroup of CTCs will survive during the harsh journey in the blood and colonise distant sites. The in-depth analysis of these metastasis-competent CTCs is very challenging because of their extremely low concentration in peripheral blood. So far, only few groups managed to expand in vitro and in vivo CTCs to be used as models for large-scale descriptive and functional analyses of CTCs. These models have shown already the high variability and complexity of the metastatic cascade in patients with cancer, and open a new avenue for the development of new diagnostic and therapeutic approaches.