Circulating Tumor Cells—New Challenges Ahead

Lianidou, Evi

doi:10.1373/clinchem.2011.180646

Cited by 29 publications

(29 citation statements)

References 15 publications

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“…In conclusion, not only do these findings point to the need for further molecular characterization of circulating epithelial cells, they also have important implications for the use of CTC testing (31,34 ).…”

Section: Circulating Epithelial Cells In Patients With Benign Diseasesmentioning

confidence: 82%

Circulating Tumor Cells: Liquid Biopsy of Cancer

2013

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BACKGROUND:The detection and molecular characterization of circulating tumor cells (CTCs) are one of the most active areas of translational cancer research, with Ͼ400 clinical studies having included CTCs as a biomarker. The aims of research on CTCs include (a) estimation of the risk for metastatic relapse or metastatic progression (prognostic information), (b) stratification and real-time monitoring of therapies, (c) identification of therapeutic targets and resistance mechanisms, and (d) understanding metastasis development in cancer patients.CONTENT: This review focuses on the technologies used for the enrichment and detection of CTCs. We outline and discuss the current technologies that are based on exploiting the physical and biological properties of CTCs. A number of innovative technologies to improve methods for CTC detection have recently been developed, including CTC microchips, filtration devices, quantitative reverse-transcription PCR assays, and automated microscopy systems. Molecularcharacterization studies have indicated, however, that CTCs are very heterogeneous, a finding that underscores the need for multiplex approaches to capture all of the relevant CTC subsets. We therefore emphasize the current challenges of increasing the yield and detection of CTCs that have undergone an epithelialmesenchymal transition. Increasing assay analytical sensitivity may lead, however, to a decrease in analytical specificity (e.g., through the detection of circulating normal epithelial cells).

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Section: Circulating Epithelial Cells In Patients With Benign Diseasesmentioning

confidence: 82%

Circulating Tumor Cells: Liquid Biopsy of Cancer

2013

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“…Besides the potential utility for targeted therapies, an additional genetic characterization of CTCs will add specificity to current CTC assays (14 ). Under certain pathological conditions such as inflammatory bowel diseases, nonmalignant epithelial cells can be released into the blood circulation, leading to false-positive CTC results unless strict morphological and molecular criteria are imposed (31 ).…”

Section: Discussionmentioning

confidence: 99%

“…This limitation might be overcome by the recently proposed use of circulating tumor cells (CTCs) as a "liquid biopsy" (13)(14)(15)(16)(17)(18). CTCs may reflect subpopulations of primary and/or metastatic tumor cells, and CTCs are easily accessible through blood collection.…”

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confidence: 99%

“…CTCs may reflect subpopulations of primary and/or metastatic tumor cells, and CTCs are easily accessible through blood collection. However, CTCs comprise only a few cells among millions of blood cells, and their detection and molecular analysis are challenging (14 ). Currently, the automated CellSearch® system (CS) is the only FDA-cleared application for CTC detection in patients with metastatic breast, colorectal, and prostate cancer (16 -18 ).…”

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confidence: 99%

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Heterogeneity of Epidermal Growth Factor Receptor Status and Mutations of KRAS/PIK3CA in Circulating Tumor Cells of Patients with Colorectal Cancer

Bauernhofer²,

et al. 2013

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“…However, simple quantification of CTCs is not enough. The molecular characterization of CTCs is absolutely necessary for advancing our understanding of the biology of metastasis and enabling us to identify patients who will benefit from targeted therapy (6 ).…”

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confidence: 99%

SOX17 Promoter Methylation in Circulating Tumor Cells and Matched Cell-Free DNA Isolated from Plasma of Patients with Breast Cancer

et al. 2013

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INTRODUCTION Detection of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) in the peripheral blood of patients with solid tumors has been widely studied for the early detection of metastatic spread. We evaluated whether there was an association between the origin of cfDNA and CTCs. We investigated whether SRY (sex determining region Y)-box 17 (SOX17) promoter methylation in CTCs was associated with the methylation pattern of this gene in matched cfDNA isolated from plasma of patients with breast cancer. METHODS We examined SOX17 methylation in 79 primary breast tumors, in 114 paired samples of DNA isolated from CTCs and cfDNA, and in 60 healthy individuals. Isolated DNA was modified by sodium bisulfite and subjected to methylation specific PCR. RESULTS The SOX17 promoter was methylated in 68 (86.0%) of 79 of primary breast tumors. In CTCs, SOX17 was methylated in 19 (34.5%) of 55 patients with early breast cancer, 27 (45.8%) of 59 patients with metastatic cancer, and 1 (4.3%) of 23 healthy individuals, whereas in matched cfDNA SOX17 was methylated in 19 (34.5%) of 55, 24 (40.7%) of 59, and 1 (2.0%) of 49 of these same groups, respectively. There was a significant correlation between SOX17 methylation in cfDNA and CTCs in patients with early breast cancer (P = 0.008), but not in patients with verified metastasis (P = 0.283). CONCLUSIONS The SOX17 promoter is highly methylated in primary breast tumors, in CTCs isolated from patients with breast cancer, and in corresponding cfDNA samples. Our findings indicate a direct connection between the presence of CTCs and cfDNA in patients with operable breast cancer, after surgical removal of the primary tumor.

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Circulating Tumor Cells—New Challenges Ahead

Cited by 29 publications

References 15 publications

Circulating Tumor Cells: Liquid Biopsy of Cancer

Circulating Tumor Cells: Liquid Biopsy of Cancer

Heterogeneity of Epidermal Growth Factor Receptor Status and Mutations of KRAS/PIK3CA in Circulating Tumor Cells of Patients with Colorectal Cancer

SOX17 Promoter Methylation in Circulating Tumor Cells and Matched Cell-Free DNA Isolated from Plasma of Patients with Breast Cancer

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