Circulating Tumor Cells and Tumor Microenvironment

Circulating Tumor Cells (CTC) and Circulating Tumor Microemboli (CTM) are cancer seeds in transit from primary to secondary soils. They thus experience a changing microenvironment from primary tumor, to blood and to metastatic sites. We review the interaction between CTC/CTM and the changing CTC/CTM microenvironments and discuss the new developments shedding light on the impact of this interaction on tumor cells growth, detachment, invasion, circulation, survival, seeding, proliferation and colonization.

The relevance of CTC/CTM stems from their key role in tumor invasion. We thus review the major issues involved in CTC and CTM tumor identity and biological characteristics, the related technical challenges for their extraction from blood, diagnostic identification and discuss their potential for clinical benefit. We analyze CTC/CTM-related methodological bias and critical issues to use CTC for bringing clinical benefit to patients, and highlight recent developments and burning questions which should be addressed to improve our understanding of this domain. We discuss the conceptual difference between CTC/CTM and Circulating Cancer Cells (CCC)/ Circulating Cancer Microemboli (CCM) and the role of CCC/CCM in tumor invasion.

Finally, we review the challenges related to the study of CCC/CCM molecular code and the relevance of their molecular characterization for a better understanding of the invasion process.

CCC/CCM are poised to bring a major improvement in the field of personalized, non-invasive predictive oncology. We will review the scientific background and developments which allow predicting this change.