Abstract
The comprehensive analysis of biological and clinical aspects of circulating tumor cells (CTCs) has attracted interest as a means of enabling non-invasive, real-time monitoring of cancer patients and enhancing our fundamental understanding of tumor metastasis. However, CTC populations are extremely small when compared to other cell populations in the blood, limiting our comprehension of CTC biology and their clinical utility. Recently developed proteomic and genomic techniques that require only a small amount of sample have attracted much interest and expanded the potential utility of CTCs. Cancer heterogeneity, including specific mutations, greatly impacts disease diagnosis and the choice of available therapeutic strategies. The CTC population consists primarily of cancer stem cells, and CTC subpopulations are thought to undergo epithelial–mesenchymal transition during dissemination. To better characterize tumor cell populations, we demonstrated that changes in genomic profiles identified via next-generation sequencing of liquid biopsy samples could be expanded upon to increase sensitivity without decreasing specificity by using a combination of assays with CTCs and circulating tumor DNA. To enhance our understanding of CTC biology, we developed a metabolome analysis method applicable to single CTCs. Here, we review―omics studies related to CTC analysis and discuss various clinical and biological issues related to CTCs.
Highlights
Cancer is the second leading cause of death in the United States [1]
We used the microfluidics flow method to enrich circulating tumor cells (CTCs) and found an average of 14.5 CTCs/mL of blood in one patient, and CTCs were observed in 27 of 31 patients enrolled in our study [62]. These results suggest that the label-free microfluidics flow method enables more efficient enrichment of CTCs that have undergone epithelial–mesenchymal transition (EMT) compared with immunoaffinity-based enrichment technologies
To enhance our understanding of CTC biology, we developed a metabolomic analysis method that can be performed with a single CTC [64]
Summary
Cancer is the second leading cause of death in the United States [1]. Comprehensive analysis of the biological and clinical aspects of circulating tumor cells (CTCs) has attracted considerable interest as a means of enabling the non-invasive, real-time monitoring of cancer patients and enhancing our fundamental understanding of tumor metastasis. The CTC population is extremely small when compared to other cell populations in the blood, limiting our understanding of their biology and clinical utility, unlike the case of tissue biopsy repeated sampling to obtain more cells is possible. This makes CTCs an ideal and clinically practical material for investigations of basic biological and clinical characteristics of cancer cells but tumor heterogeneity and drug resistance as well [14].
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