Circulating Tumor Stem Cells as Biomarkers for Cancer Progression
Olatz Leis, Paz Lopez-Mato and Angel G. Martin
Affiliation: Fundacion Inbiomed, P.Mikeletegi 81, San Sebastian 20009 Spain.
Keywords: Circulating tumor cells, Cytokeratin, EpCam, Her2, EMT, Prognosis, adhesion molecules, CSC associated biomarkers, Clinical trials, EGFR
The identification of a minor cellular subpopulation responsible for the initiation, maintenance and expansion of tumors (the cancer stem cells -CSCs-) meant a radical paradigm shift, but at the same time the selection of specific biomarkers may have extraordinary prognostic value. Recently, circulating epithelial cells (CTCs) have been identified in peripheral blood of solid tumor patients, demonstrating their prognostic value in metastatic breast cancer and positive predictive value for treatment response. This identification is based on epithelial cell markers in peripheral blood through immunocytochemistry technology or PCR, with a clear prognostic goal. Since CSCs are responsible for the initiation of new tumor lesions, we propose that a subpopulation of CTCs is the CSCs that will initiate metastasis. It is reasonable to speculate that a subpopulation of CTCs with stem cell features, such as self-renewal, multipotency, tumorigenicity and likely showing markers of epithelial-mesenchymal transition (EMT), may be the relevant players during metastasis. Further research into molecular characterization of CSC specific CTCs will create opportunities for novel therapeutic intervention, but at the same time facilitate the detection of clinically relevant CTCs. In this review, recent patents on CTC biomarkers are summarized.
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