Circulating Tumor Cell Detection Technologies and Clinical Utility: Challenges and Opportunities

Abstract

The potential clinical utility of circulating tumor cells (CTCs) in the diagnosis and management of cancer has drawn a lot of attention in the past 10 years. CTCs disseminate from tumors into the bloodstream and are believed to carry vital information about tumor onset, progression, and metastasis. In addition, CTCs reflect different biological aspects of the primary tumor they originate from, mainly in their genetic and protein expression. Moreover, emerging evidence indicates that CTC liquid biopsies can be extended beyond prognostication to pharmacodynamic and predictive biomarkers in cancer patient management. A key challenge in harnessing the clinical potential and utility of CTCs is enumerating and isolating these rare heterogeneous cells from a blood sample while allowing downstream CTC analysis. That being said, there have been serious doubts regarding the potential value of CTCs as clinical biomarkers for cancer due to the low number of promising outcomes in the published results. This review aims to present an overview of the current preclinical CTC detection technologies and the advantages and limitations of each sensing platform, while surveying and analyzing the published evidence of the clinical utility of CTCs.

Current Status and Future Perspectives of Liquid Biopsy in Small Cell Lung Cancer

“…These technologies can be categorized based on the method of isolation as label-dependent (affinity-based) or label-independent [ 90 ] ( Figure 3 A). The label-dependent methods are the most commonly used approaches and are based on the expression of cell surface markers (such as EpCAM).…”

“…However, this approach has the limitation of only isolating CTCs based on EpCAM expression, ignoring other low epithelial CTCs [ 93 ]. On the other hand, label-independent approaches allow the isolation of CTCs with a low epithelial phenotype because these platforms discriminate CTCs from other cells based on physical characteristics such as size, density, deformability and electrical properties [ 90 ]. For example, there are size-based separation methods [ 94 ] (filter-based detection, microfluidic chips, centrifugal forces or inertial focusing) and direct imaging and biophysical property-based methods [ 90 , 95 ].…”

The Polemic Diagnostic Role of TP53 Mutations in Liquid Biopsies from Breast, Colon and Lung Cancers

“…With respect to CTCs, the methodology used for isolation and subsequent analysis also has an impact on the cost–benefit balance of their application. Highly standardized FDA-approved technologies such as CellSearch have demonstrated their clinical utility [ 94 ], however there is still room for better phenotypic characterization and cost reduction; in fact, other platforms such as microfluidic-based ones are reducing reagents costs and improving performance [ 95 ] and might become more affordable in the near future.…”

Dangerous Liaisons: Circulating Tumor Cells (CTCs) and Cancer-Associated Fibroblasts (CAFs)

“…However, the isolation and characterization of CTCs have been hampered mainly by the combination of two factors, their low frequency in the blood of cancer patients, and until recently, the limited access to a technology capable of enriching few CTCs from a large background of blood cells. In recent years, many different assays were developed for the identification, enumeration, and characterization of CTCs [ 20 ]. CTC-enrichment technologies are broadly classified in two groups.…”