Circulating tumor cells: Back to the future

Circulating tumor cells (CTCs) are rare and heterogeneous cells found in the peripheral blood of cancer patients. They are supposed to be a central component of metastatic dissemination and have been correlated with prognosis, progression-free survival, and treatment efficacy in different solid tumors (1, 2). Despite CTC significance, studies conducted on them still present considerable issues. In particular, regarding to how CTCs should be investigated and to their actual metastatic competence and tumor heterogeneity reflecting dissimilar cancer cell subpopulations. Importantly, CTCs’ clinical utility has not been demonstrated and they cannot be utilized to guide therapeutic decisions. As reviewed by others (3), recent and currently ongoing clinical trials are trying to deter- mine the predictive role of CTCs, but they are apparently failing to support definitive conclusions. Nevertheless, the results of these trials could shed a light on the real possibilities of CTCs. In our opinion, CTC troubleshootings will depend on what scientific community will explore about CTCs and the metastatic process. Only a deeper insight in base knowledge about CTCs and their role in tumor biology may help us in overcoming such hurdles.