Evaluation of circulating tumor cells (CTCs) has demonstrated clinical validity as a prognostic tool based on enumeration, but since the introduction of this tool to the clinic in 2004, further clinical utility and widespread adoption have been limited. However, immense efforts have been undertaken to further the understanding of the mechanisms behind the biology and kinetics of these rare cells, and progress continues toward better applicability in the clinic. This review describes recent advances within the field, with a particular focus on understanding the biological significance of CTCs, and summarizes emerging methods for identifying, isolating, and interrogating the cells that may provide technical advantages allowing for the discovery of more specific clinical applications. Included is an atlas of high-definition images of CTCs from various cancer types, including uncommon CTCs captured only by broadly inclusive nonenrichment techniques.

Biomedical Center Faculty of Medicine in Pilsen Charles University Prague 323 00 Pilsen Czech Republic

Bridge Institute Dornsife College of Letters Arts and Sciences University of Southern California Los Angeles California 90089; email

Department of Biomedical Engineering Viterbi School of Engineering University of Southern California Los Angeles California 90089

Department of Histology and Embryology Faculty of Medicine in Pilsen Charles University Prague 301 00 Pilsen Czech Republic

Scripps Clinic Medical Group Scripps Clinic La Jolla California 92121

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