Biomarkers for the detection of circulating tumor cells

Circulating tumor cells (CTCs) have emerged as a key biomarker in cancer detection and prognosis, and their molecular profiling is gaining importance in precision oncology. Liquid biopsies, which allow the extraction of CTCs, circulating tumor DNA (ctDNA) or cell-free DNA (cfDNA), have measurable advantages over traditional tissue biopsies, especially when molecular material is difficult to obtain. However, this method is not without limitations. Difficulties in differentiating between primary and metastatic lesions, uncertain predictive values and the complexity of the biomarkers used can prove challenging. Recently, high cell heterogeneity has been identified as the main obstacle to achieving high diagnostic accuracy. Because not all cells undergo epithelial-mesenchymal transition (EMT) at the same time, there is a large population of hybrid CTCs that express both epithelial and mesenchymal markers. Since traditional diagnostic tools primarily detect epithelial markers, they are often unable to detect cells with a hybrid phenotype; therefore, additional markers may be required to avoid false negatives. In this review, we summarize recent reports on emerging CTCs markers, with particular emphasis on their use in cancer diagnosis. Most of them, including vimentin, TWIST1, SNAI1, ZEB1, cadherins, CD44, TGM2, PD-L1 and GATA, hold promise for the detection of CTCs, but are also implicated in cancer progression, metastasis, and therapeutic resistance. Therefore, understanding the nature and drivers of epithelial-mesenchymal plasticity (EMP) is critical to advancing our knowledge in this field.