Profiling circulating tumour cells and other biomarkers of invasive cancers
Mahla Poudineh1, Edward H. Sargent, Klaus Pantel and Shana O. Kelley
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 meta-static potential of CTCs, and for the meaningful analysis of circulating tumour DNA and exosomes.
Circulating tumour cells (CTCs) and other cancer-related biomarkers are present in the blood of many patients with cancer. CTCs are believed to be involved in the formation of metastatic tumours. Indeed, high CTC levels in the bloodstream are associated with poor prognosis and an increased probability of metastatic disease1–4. It was initially thought that the formation of metastatic lesions occurs in the later stages of cancer progression. However, recent studies have shown that CTCs can leave primary tumours and enter into the circulation at a relatively early stage of tumour growth5,6. This can lead to the parallel development of met-astatic lesions and primary tumours. The study of CTCs is there-fore central to the study of the mechanism of cancer metastasis, and the analysis of CTCs and other circulating biomarkers in clinical specimens provides a basis for the development of non-invasive liquid biopsies.