Abstract
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 determine 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.
Highlights
Circulating tumor cells (CTCs) are rare and heterogeneous cells found in the peripheral blood of cancer patients
Despite the pivotal results obtained with this system [6,7,8,9], its detection approach, based on epithelial markers only, fails to reflect all the potential CTC subpopulations, e.g., EpCAM-negative cells [10]
The lack in technical standardization still hinders CTCs’ full translation in the clinical practice, these alternative methods could shed a light on the true nature of CTCs and pave the way to a clearer window into cancer biology and metastasis
Summary
Regarding to how CTCs should be investigated and to their actual metastatic competence and tumor heterogeneity reflecting dissimilar cancer cell subpopulations. Despite the pivotal results obtained with this system [6,7,8,9], its detection approach, based on epithelial markers only, fails to reflect all the potential CTC subpopulations, e.g., EpCAM-negative cells [10]. In order to get further key insights into tumor aggressiveness, metastatic competence, heterogeneity, and resistance to treatment, we have to look back more deeply at base research, i.e., CTC-related epithelial–mesenchymal transition and stemness, CTC subpopulation/heterogeneity, and to CTC preclinical ex vivo studies.
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