Cancer Stem Cells and Circulating Tumor Cells: Molecular Markers, Isolation Techniques, and Clinical Implications

Abstract

There is now a considerable body of evidence that many cancers are hierarchically organized and driven by a cellular component termed “cancer stem cells” (CSCs). These cells have the ability to self-renew and to generate heterogeneous populations that constitute the tumor bulk. Preclinical studies have demonstrated that CSCs mediate tumor metastasis and resistance to chemotherapy and radiation therapy. CSC biomarkers have been identified and both in vitro and mouse models have been developed to facilitate the isolation of these cells as well as the elucidation of CSC regulatory pathways. Agents targeting CSCs have now entered early phase clinical trials. The development of these clinical trials highlights the important need to develop technologies to monitor CSCs in patients. Unlike hematologic malignancies, where tumor specimens are readily obtainable, in solid tumors obtaining serial biopsies to assess CSCs is difficult. Studies suggest that circulating tumor cells (CTCs) contain a highly enriched proportion of CSCs and thus monitoring these cells in blood may provide a liquid biopsy for CSC assessment in solid tumors. In parallel with developments of efficient CTC isolation technologies, assays to molecularly characterize these cells at single cell resolution are also being developed. In this chapter we will review the current status of CSC therapeutic technologies as well as microfluidic techniques for isolation and molecular characterization of CTCs in cancer patients. If CSCs are responsible for tumor metastasis, resistance, and recurrence, development of effective CSC therapies has the potential to significantly improve the efficacy of cancer treatments.