Abstract

Circulating tumor cells (CTCs) can be detected in the blood of different types of early or advanced cancer using immunology-based assays or nucleic acid methods. The detection and quantification of CTCs has significant clinical utility in the prognosis of metastatic breast, prostate, and colorectal cancers. CTCs are a heterogeneous population of cells and often different from those of their respective primary tumor. Understanding the biology of CTCs may provide useful predictive information for the selection of the most appropriate treatment. Therefore, CTC detection and characterization could become a valuable tool to refine prognosis and serve as a “real-time biopsy” and has the potential to guide precision cancer therapies, monitor cancer treatment, and investigate the process of metastasis.

Highlights

  • Circulating tumor cells (CTCs) were first observed in the late 19th century [1]

  • 86% of metastatic breast cancer (MBC) patients expressed one or more multidrug resistance-related proteins (MRPs); patients with MRP-positive CTCs had shorter times to progression. These findings suggest that a pool of CTCs may exhibit some stem cell-like properties that contribute to metastatic spread and drug resistance

  • Methods of CTC detection are broadly divided into nucleic-acid based approaches (PCR targeting of various epithelial mRNAs, cytokeratins (CKs) [8] and epithelial cell adhesion molecule (EpCAM)), immunology-based, and epithelial immunospot (EPISPOT) assays

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Summary

Introduction

Circulating tumor cells (CTCs) were first observed in the late 19th century [1]. Methods for the detection of CTCs in the peripheral blood of patients with epithelial tumors (including breast [2,3], colorectal [4,5], prostate [6] and lung [7]) have recently been developed. Armstrong and colleagues [28] found that the majority of CTCs in patients with metastatic prostate and metastatic breast cancer co-express epithelial proteins (EpCAM, CK, E-cadherin) and mesenchymal proteins, including vimentin and N-cadherin. Subpopulations of CTCs may demonstrate a stem cell-like phenotype that might contribute to the metastatic spread of primary tumors and resistance to conventional chemotherapy. 86% of metastatic breast cancer (MBC) patients expressed one or more multidrug resistance-related proteins (MRPs); patients with MRP-positive CTCs had shorter times to progression. These findings suggest that a pool of CTCs may exhibit some stem cell-like properties that contribute to metastatic spread and drug resistance. The EPISPOT assay could be effective in evaluating more accurate CTC counts based on viability, but this test has not, to date, been evaluated in large-scale clinical trials or undergone formal commercial development

CTC Detection and Quantification
Enrichment and Capture of CTCs
Nucleic Acid-Based Methods
Immunological-Based Assay
Clinical Manifestation of CTCs
Clinical Application of CTCs
CTC Enumeration in Patients with Early-Stage Disease
CTCs’ Enumeration in Patients with Metastatic Disease
Perspectives
Conclusions
Full Text
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