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.

Sequential Isolation and Characterization of Single CTCs and Large CTC Clusters in Metastatic Colorectal Cancer Patients

“…The inappropriateness of standard CTCs isolation devices for clusters isolation and the scarce availability of detection methods able to specifically isolate and characterize both single CTCs and CTC clusters finally banned in-depth studies on the prognostic and predictive value of clusters in clinical practice, unlike that which has been described for single CTCs. Although evidence has been provided that size-exclusion assays, such as blood filtration, would represent an affordable approach for CTC clusters isolation, only few filtration devices can simultaneously detect single and clustered CTCs starting from a single blood sample [ 17 ]. Here we used a sequential filtration-based approach to investigate the simultaneous presence of single CTCs and CTC clusters in a small group of patients with metastatic colorectal cancer.…”

Emerging Lab-on-a-Chip Approaches for Liquid Biopsy in Lung Cancer: Status in CTCs and ctDNA Research and Clinical Validation

“…While some depend on biochemical properties and biological signature of CTCs (affinitybased strategies), others are constructed based on their biophysical properties (label-free strategies), compared to blood cells (Figure 2) [68][69][70][71]. A thorough review regarding technologies for CTCs enrichment has recently been published by Rushton et al [72]. Separation based on biochemical properties of CTCs depends on specific bonding between tumor-specific antigens on the surface of cells and complementary ligands added and fixed along the microfluidic platform.…”

Challenging the Current Paradigm of Liquid Biopsy Through Dielectrophoresis (DEP) In Prostate Cancer

“…In this context, liquid biopsy via isolation of CTCs represents a promising diagnostic tool capable of supplementing state-of-the-art PC diagnostics 39 and prognosis [40][41][42][43][44] .…”