Circulating Tumor Cells: Liquid Biopsy of Cancer
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TLDR
A considerable number of promising CTC-detection techniques have been developed in recent years, but the analytical specificity and clinical utility of these methods must be demonstrated in large prospective multicenter studies to reach the high level of evidence required for their introduction into clinical practice.Abstract:
BACKGROUND: The detection and molecular characterization of circulating tumor cells (CTCs) are one of the most active areas of translational cancer research, with >400 clinical studies having included CTCs as a biomarker. The aims of research on CTCs include ( a ) estimation of the risk for metastatic relapse or metastatic progression (prognostic information), ( b ) stratification and real-time monitoring of therapies, ( c ) identification of therapeutic targets and resistance mechanisms, and ( d ) understanding metastasis development in cancer patients.
CONTENT: This review focuses on the technologies used for the enrichment and detection of CTCs. We outline and discuss the current technologies that are based on exploiting the physical and biological properties of CTCs. A number of innovative technologies to improve methods for CTC detection have recently been developed, including CTC microchips, filtration devices, quantitative reverse-transcription PCR assays, and automated microscopy systems. Molecular-characterization studies have indicated, however, that CTCs are very heterogeneous, a finding that underscores the need for multiplex approaches to capture all of the relevant CTC subsets. We therefore emphasize the current challenges of increasing the yield and detection of CTCs that have undergone an epithelial–mesenchymal transition. Increasing assay analytical sensitivity may lead, however, to a decrease in analytical specificity (e.g., through the detection of circulating normal epithelial cells).
SUMMARY: A considerable number of promising CTC-detection techniques have been developed in recent years. The analytical specificity and clinical utility of these methods must be demonstrated in large prospective multicenter studies to reach the high level of evidence required for their introduction into clinical practice.read more
Citations
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Circulating Tumor Cell Clusters Are Oligoclonal Precursors of Breast Cancer Metastasis
Nicola Aceto,Aditya Bardia,David T. Miyamoto,Maria C. Donaldson,Ben S. Wittner,Joel A. Spencer,Min Yu,Adam Pely,Amanda Engstrom,Huili Zhu,Brian W. Brannigan,Ravi Kapur,Shannon L. Stott,Toshi Shioda,Sridhar Ramaswamy,David T. Ting,Charles P. Lin,Mehmet Toner,Daniel A. Haber,Daniel A. Haber,Shyamala Maheswaran +20 more
TL;DR: Using mouse models with tagged mammary tumors, it is demonstrated that CTC clusters arise from oligoclonal tumor cell groupings and not from intravascular aggregation events, and though rare in the circulation, they greatly contribute to the metastatic spread of cancer.
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TL;DR: What is known about circulating tumor cells, their clinical potential as biomarkers and therapeutic targets, and future research directions that may help realize theirclinical potential are discussed.
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