Circulating Tumor Cells: Technologies and Their Clinical Potential in Cancer Metastasis

Abstract

Circulating tumor cells (CTCs) are single cells or clusters of cells within the circulatory system of a cancer patient. While most CTCs will perish, a small proportion will proceed to colonize the metastatic niche. The clinical importance of CTCs was reaffirmed by the 2008 FDA approval of CellSearch®, a platform that could extract EpCAM-positive, CD45-negative cells from whole blood samples. Many further studies have demonstrated the presence of CTCs to stratify patients based on overall and progression-free survival, among other clinical indices. Given their unique role in metastasis, CTCs could also offer a glimpse into the genetic drivers of metastasis. Investigation of CTCs has already led to groundbreaking discoveries such as receptor switching between primary tumors and metastatic nodules in breast cancer, which could greatly affect disease management, as well as CTC-immune cell interactions that enhance colonization. In this review, we will highlight the growing variety of isolation techniques for investigating CTCs. Next, we will provide clinically relevant context for CTCs, discussing key clinical trials involving CTCs. Finally, we will provide insight into the future of CTC studies and some questions that CTCs are primed to answer.

Identifying drivers of breast cancer metastasis in progressively invasive subpopulations of zebrafish-xenografted MDA-MB-231

“…We consider these cells analogous to circulating tumor cells (CTCs). CTCs are a unique population of tumor cells that invade the basement membrane and intravasate into the vasculature, serving as the source of cells from which metastatic nodules will eventually form [ 26 ]. In this model, only those MDA-MB-231 cells that have the capacity to invade the basement membrane, intravasate into the zebrafish vasculature, and migrate using the circulatory system are monitored and studied.…”

“…In this study, we used xenografted zebrafish embryos to identify two subpopulations of MDA-MB-231 breast cancer cells that exhibited progressively invasive behavior. These populations are analogous to circulating tumor cells found in human cancers [ 25 , 26 ]. Differential gene analysis of these subpopulations with their parental population revealed activation of an epithelial-mesenchymal transition (EMT) program as well as enrichment of several pathways consistent with prior reports of breast cancer metastasis.…”

Preoperative Folate Receptor-Positive Circulating Tumor Cells Are Associated With Occult Peritoneal Metastasis and Early Recurrence in Gastric Cancer Patients: A Prospective Cohort Study

“…The most widely reported and the only Food and Drug Administration (FDA)-approved technique to detect CTC and CTC cluster level was CellSearch™ System. CellSearch™ System (Menarini Silicon Biosystems Inc., Huntingdon Valley, PA, USA) is an antibody-based marker-dependent platform that applied immunomagnetic separation and flow cytometry protocol to detect CTCs in peripheral blood ( 58 ). No studies directly compare the sensitivity and specificity of different CTC detection methods.…”

The current state of molecular profiling in gastrointestinal malignancies

“…It has been shown that CTCs are an intermediate stage of cancer metastasis. Like ctDNA, CTCs are obtained from peripheral blood; however, CTCs may have a greater clinical impact as they can be grown, propagated, and extensively studied in vitro and in vivo under optimal conditions [ 208 , 209 ]. However, it is unclear if a single cell assay accurately reflects entire tumor heterogeneity.…”