Liquid biopsy-based colorectal cancer screening via surface markers of circulating tumor cells

Colorectal cancer (CRC) is ranked second for cancer-related deaths worldwide with ap-proximately 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 intro-duction 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 assess-ment, 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.