Importance and detection of epithelial-to-mesenchymal transition (EMT) phenotype in CTCs

The current dogma is that epithelial-to-mesenchymal transition (EMT) promotes circulating tumour cell (CTC) formation and is ultimately a driver of metastasis. There is also accumulating evidence that EMT-phenotype changes are commonly associated with therapy resistance. Thus, capturing EMT-phenotype CTCs is expected to yield important clinical information in regard to prognosis and response to therapy as well as allowing the study of metastatic processes. However, the isolation and identification of EMT-phenotype CTCs with commonly used isolation/detection methods are suboptimal, and current efforts on improving the isolation of EMT-phenotype CTCs are associated with pitfalls that need to be overcome. This chapter explores the significance of EMT in CTC formation and the role of EMT in cancer metastasis and resistance to therapy. We also comprehensively review the past and current limitations of evaluating EMT phenotypes in CTC isolation and analysis and discuss how CTCs can be seen in a more holistic fashion as important biomarkers for clinical management.