Mesenchymal Characteristics and Predictive Biomarkers on Circulating Tumor Cells for Therapeutic Strategy

SIMPLE SUMMARY: Circulating tumor cells (CTCs) are the seeds that spread through the circulatory system and generate the metastatic sites. Among the various phenotypes exhibited by CTCs, epithelial-to-mesenchymal transition (EMT) has extensively gained attention because of its contribution to the acquisition of invasiveness and motility of CTCs, which is critical for the successful metastasis process. So far, many clinical studies have demonstrated that expressions of mesenchymal features in CTCs are associated with poor clinical outcomes in many types of solid cancer. In this review, the clinical significance of CTCs as a liquid biopsy is described in terms of the mesenchymal characteristics, expression of predictive biomarkers, and their correlations. Detailed analysis of these multivariate targets in CTCs could improve therapeutic decision-making. ABSTRACT: Metastasis-related events are the primary cause of cancer-related deaths, and circulating tumor cells (CTCs) have a pivotal role in metastatic relapse. CTCs include a variety of subtypes with different functional characteristics. Interestingly, the epithelial–mesenchymal transition (EMT) markers expressed in CTCs are strongly associated with poor clinical outcome and related to the acquisition of circulating tumor stem cell (CTSC) features. Recent studies have revealed the existence of CTC clusters, also called circulating tumor microemboli (CTM), which have a high metastatic potential. In this review, we present current opinions regarding the clinical significance of CTCs and CTM with a mesenchymal phenotype as clinical surrogate markers, and we summarize the therapeutic strategy according to phenotype characterization of CTCs in various types of cancers for future precision medicine.