Abstract

Colorectal cancer (CRC) is ranked second for cancer-related deaths worldwide with approximately half of the patients being diagnosed at the late stages. The untimely detection of CRC results in advancement to the metastatic stage and nearly 90% of cancer-related deaths. The early detection of CRC is crucial to decrease its overall incidence and mortality rates. The recent introduction of circulating tumor cells (CTCs) has enabled a less invasive sampling method from liquid biopsies, besides revealing key information toward CRC metastasis. The current gold standard for CTC identification is the CellSearch® system (Veridex). This first-generation instrumentation relies on a single cell surface marker (CSM) to capture and count CTCs. Detection of CTCs allows the identification of patients at risk for metastasis, whereas CTC enumeration could improve risk assessment, monitoring of systemic therapy, and detection of therapy resistance in advanced metastatic CRC. In this review, we compared the pros and cons between single CSM-based CTC enrichment techniques and multi-marker-based systems. We also highlighted the challenges faced in the routine implementation of CSM-dependent CTC detection methods in CRC screening, prediction, prognosis, disease monitoring, and therapy selection toward precision medicine, as well as the dwelling on post-CTC analysis and characterization methods.

Highlights

  • Colorectal cancer (CRC) is among the most common global health issues with a startling surge in incidence (10.2%) and mortality (9.2%) rates [1]

  • Circulating tumor cells (CTCs) denote epithelial cancer cells found in the bloodstream [21,22,23]

  • Targeting epithelial cell adhesion molecule (EpCAM) on circulating tumor cells (CTCs) from CRC seems to be the best option to distinguish between CTCs and normal blood cells with mesenchymal phenotypes, the overreliance on a single specific cell surface marker (CSM) resulted in a selection bias [79], where only CTCs that predominantly retain epithelial characteristics are enriched, excluding a subpopulation of CTCs with mesenchymal traits

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Summary

Introduction

Colorectal cancer (CRC) is among the most common global health issues with a startling surge in incidence (10.2%) and mortality (9.2%) rates [1]. The former is the most sensitive procedure for CRC diagnosis as it permits the visualization and removal/surgery of colorectal tumors and pre-cancerous lesions (adenomas and polyps) [9,10] When coupled with the latter, analysis of the excised tumors is possible, classifying them into different tumor stages/groups based on their clinicopathological features for better treatment selections [11]. Circulating tumor cells (CTCs) denote epithelial cancer cells found in the bloodstream [21,22,23] Their detection differs drastically from person to person but is often observed in patients with metastatic CRC (mCRC) [24,25,26,27].

Existing Blood-based Biomarkers Are Not Effective with Low Accuracy
Single Specific CSM-based CTC Enrichment Strategy Had Its Limitations
Alternative CSMs and Multiplexing Show Potential in Targeting a Wider
Circulating Cancer Stem Cells Are a Rare CTC Subtype
Stigma on Circulating Tumor Markers in Blood
10. Challenges in Routine Implementation of CTC-Specific CSM-dependent
Findings
11. Conclusions
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