Identification and Quantitation of Circulating Tumor Cells

Abstract

Circulating tumor cells (CTCs) are shed from the primary tumor into the circulatory system and act as seeds that initiate cancer metastasis to distant sites. CTC enumeration has been shown to have a significant prognostic value as a surrogate marker in various cancers. The widespread clinical utility of CTC tests, however, is still limited due to the inherent rarity and heterogeneity of CTCs, which necessitate robust techniques for their efficient enrichment and detection. Significant recent advances have resulted in technologies with the ability to improve yield and purity of CTC enrichment as well as detection sensitivity. Current efforts are largely focused on the translation and standardization of assays to fully realize the clinical utility of CTCs. In this review, we aim to provide a comprehensive overview of CTC enrichment and detection techniques with an emphasis on novel approaches for rapid quantification of CTCs.

Circulating Tumor Cells in Gastrointestinal Cancers: Current Status and Future Perspectives

“…By contrast, PCR-based molecular assays provide objective and quantifiable CTCs measurements with the advantages of automated, sensitive, relatively low-cost and amenable to quantifiable quality control. Moreover, these methods require a small amount of cells for analysis, which is also in line with the fact that the amount of CTCs is less (51). However, since the molecular characterization of CTCs by PCR assays is based on the detection of mRNA markers that are specifically expressed in CTCs but not in leukocytes, the risk of false-positive results might be increased due to the non-specific amplification of RNA (50)(51)(52).…”

Circulating Tumor Cells in the Parallel Invasion Model Supporting Early Metastasis

“…[18] CTCs are shed from the primary tumor into the circulatory system and act as seeds that initiate cancer metastasis to distant sites. [9] CTCs are rare among blood cells and need to be enriched for further analysis by marker-dependent and -independent methods. The most advanced system for clinical use is the CellSearch© system which relies on immunomagnetic separation of EpCAM-positive tumor cells and confirmation of their cancer origin by proof of expression of cytokeratins and absence of the leucocyte marker CD45.…”

“…The multitude of methods to capture CTCs are described in a large number of comprehensive reviews. [9,20,21] In addition to CTCs, circulating tumor microemboli (CTM)/CTC clusters, CTM-associated materials (CTMat) and circulating free DNA can be detected in cancer patients. [22] The essential result of the assessment of CTCs in cancer patients is the correlation of higher CTC counts with lower disease-free survival and poorer prognosis as well as a correlation of the decrease of the CTC counts with effective chemotherapy.…”

“…Research has focused on the sensitive detection of the rare CTCs using approaches depending on cell surface markers or physical properties of the cancer cells. [9] A host of techniques Ivyspring International Publisher has been described with the CellSearch© system, which selects peripheral cancer cells according to their expression of EpCAM, the single method approved by the FDA so far. [10] CTCs counts were demonstrated to have prognostic significance in several tumor types and an increase under cytotoxic therapy correlates with the resistance to treatment.…”

Challenges and unanswered questions for the next decade of circulating tumour cell research in lung cancer

“…We will reference CTC studies across all cancer types but will highlight studies addressing lung cancer CTCs. Given the broad scope of CTC research and the large numbers of CTC publications we cannot provide an exhaustive coverage of the subject so for those requiring more detail we would recommend recent excellent CTC reviews (7)(8)(9).…”