Characterization of single circulating tumor cells

Abstract

"Liquid biopsy" has been introduced for the analysis of circulating tumor cells (CTCs) in the blood of cancer patients, and this new diagnostic approach has received enormous attention. CTCs are derived from primary tumors and metastatic lesions and, therefore, harbor important information on the molecular characteristics relevant to tumor progression and cancer therapy. Analyses of CTCs have paved new diagnostic avenues with obvious clinical implications for personalized medicine. Key areas of clinical applications of CTCs include detection of cancer, prediction of prognosis in patients with curable disease, monitoring systemic therapies, and stratification of patients based on the detection of therapeutic targets or resistance mechanisms. The present Review will focus on the current knowledge derived from single-cell analysis of CTCs at the DNA, RNA, and protein level and emphasize the unique opportunities for performing functional studies that aim to identify the metastasis-initiator cells in cancer patients and obtain predictive information for steering cancer therapies.

Circulating tumour cells and DNA as liquid biopsies in gastrointestinal cancer

“…The metastatic process is inefficient and most CTCs die within hours. Yet, a small subset of CTCs have tumour‐initiating capacity that may be characterized at the single‐cell level in terms of molecular characteristics and tumorigenicity.…”

“…Each enrichment technique may capture different CTC populations, illustrating the need for standardized methods for clinical use. Moreover, as different CTC populations may have different clinical impact, techniques that include molecular characterization of the CTCs may be preferable.…”

Prediagnostic detection of mesothelioma by circulating calretinin and mesothelin – a case-control comparison nested into a prospective cohort of asbestos-exposed workers

“…described a promising multi-analyte blood test for a number of different cancers 15 . Such tests are also known as ‘liquid biopsies’, a term originally coined for the analysis of circulating tumor cells but increasingly used for circulating DNA, RNA, and other markers as well 16 . Many blood-based tumor markers have also been described for MM but most of them only in relatively small case-control studies with cross-sectional design or without verification in an independent study population.…”

Visual Quantitative Detection of Circulating Tumor Cells with Single‐Cell Sensitivity Using a Portable Microfluidic Device

“…CTC enrichment is the isolation of CTCs from the vast background of normal blood cells using size, density, charge, deformability, or biological properties . Most of the current CTC detection approaches involve immunocytological assays (immunocytochemistry, flow cytometry, CellSearch system, DEPArray), molecular identification (real‐time quantitative polymerase chain reaction (RT‐qPCR), enzyme‐linked immunosorbent assay (ELISA), fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH)), or functional characterization (in vitro cell culture, invasion assay, xenotransplantation models) . Unfortunately, most of them rely on high‐tech instrumentation and highly skilled personnel.…”