During cancer progression, many tumours shed circulating tumour cells (CTCs) and other biomarkers into the bloodstream. The analysis of CTCs offers the prospect of collecting a liquid biopsy from a patient’s blood to predict and monitor therapeutic responses and tumour recurrence. In this Review, we discuss progress towards the isolation and recovery of bulk CTCs from whole blood samples for the identification of cells with high metastatic potential. We provide an overview of the techniques that initially pointed to the clinical significance of CTCs and describe the key requirements for clinical applications of CTC analysis. We also summarize recent advances that permit the functional and biochemical phenotypes of CTCs to be characterized, and discuss the potential roles of these CTC characteristics in the formation of metastatic lesions. Moreover, we discuss the use of circulating tumour DNA and exosomes as markers for early cancer diagnosis and for the monitoring of cancer progression. Next-generation technologies and biomarkers for invasive cancers should allow for the unequivocal determination of the metastatic potential of CTCs, and for the meaningful analysis of circulating tumour DNA and exosomes.
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S.O.K. acknowledges the Canadian Institutes of Health Research, the National Science and Engineering Research Council, the National Institutes of Health, and the Ontario Research Fund for their support of work in this area. K.P. acknowledges European Research Council Advanced Investigator Grant DISSECT, European Research Council Proof of Concept grant CTCapture_2.0 and European Union–Innovative Medicines Initiative grant CANCER-ID for support.
S.O.K., M.P. and E.H.S. are inventors on patents related to technologies for liquid biopsy and rare-cell profiling. The other authors declare no competing financial interests.
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Poudineh, M., Sargent, E.H., Pantel, K. et al. Profiling circulating tumour cells and other biomarkers of invasive cancers. Nat Biomed Eng 2, 72–84 (2018). https://doi.org/10.1038/s41551-018-0190-5
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