A Review of Circulating Tumour Cell Enrichment Technologies

Abstract

Circulating tumour cells (CTCs) are the precursor cells for the formation of metastatic disease. With a simple blood draw, liquid biopsies enable the non-invasive sampling of CTCs from the blood, which have the potential to provide important insights into cancer detection and monitoring. Since gaining FDA approval in 2004, the CellSearch system has been used to determine the prognosis of patients with metastatic breast, prostate and colorectal cancers. This utilises the cell surface marker Epithelial Cell Adhesion Molecule (EpCAM), to enrich CTCs, and many other technologies have adopted this approach. More recently, the role of mesenchymal-like CTCs in metastasis formation has come to light. It has been suggested that these cells are more aggressive metastatic precursors than their epithelial counterparts; however, mesenchymal CTCs remain undetected by EpCAM-based enrichment methods. This has prompted the development of a variety of 'label free' enrichment technologies, which exploit the unique physical properties of CTCs (such as size and deformability) compared to other blood components. Here, we review a wide range of both immunocapture and label free CTC enrichment technologies, summarising the most significant advantages and disadvantages of each. We also highlight the important characteristics that technologies should possess for routine clinical use, since future developments could have important clinical implications, with the potential to direct personalised therapies for patients with cancer.

Keywords: cancer; circulating tumour cell (CTC); liquid biopsy; metastasis.

Figure 1

Summary of circulating tumour cell (CTC) enrichment technologies. (A) Immunocapture methods including immunomagnetic positive and negative enrichment methods, microfluidic immunocapture methods, nanomaterial immunocapture enhancement and their relevant technologies; (B) Biophysical property enrichment methods including membrane filtration, size-based microfluidics, density based and dielectrophoresis and associated technologies; (C) Other methods including in vitro, combined and secondary isolation methods and associated technologies.