Metastases and cancer recurrence are the main causes of cancer death. Circulating Tumor Cells (CTCs) and disseminated tumor cells are the drivers of cancer cell dissemination. The assessment of CTCs’ clinical role in early metastasis prediction, diagnosis, and treatment requires more information about their biology, their roles in cancer dormancy, and immune evasion as well as in therapy resistance. Indeed, CTC functional and biochemical phenotypes have been only partially characterized using murine metastasis models and liquid biopsy in human patients. CTC detection, characterization, and enumeration represent a promising tool for tailoring the management of each patient with cancer. The comprehensive understanding of CTCs will provide more opportunities to determine their clinical utility. This review provides much-needed insights into this dynamic field of translational cancer research.

In the last few decades, the epithelial cell adhesion molecule (EpCAM) has received increased attention as the main membrane marker used in many enrichment technologies to isolate circulating tumor cells (CTCs). Although there has been a great deal of progress in the implementation of EpCAM-based CTC detection technologies in medical settings, several issues continue to limit their clinical utility. The biology of EpCAM and its role are not completely understood but evidence suggests that the expression of this epithelial cell-surface protein is crucial for metastasis-competent CTCs and may not be lost completely during the epithelial-to-mesenchymal transition. In this review, we summarize the most significant advantages and disadvantages of using EpCAM as a marker for CTC enrichment and its potential biological role in the metastatic cascade.

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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.