Circulating tumor cells: Advances in isolation and analysis, and challenges for clinical applications

Harouaka, Ramdane; Kang, Zhigang; Zheng, Shan; Cao, Liang

doi:10.1016/j.pharmthera.2013.10.004

Cited by 168 publications

(149 citation statements)

References 145 publications

(222 reference statements)

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“…[4][5][6] Hence, sensitive isolation and insightful molecular characterization of CTCs could assist as a "liquid biopsy" and aid to improve individual treatment regimens for cancer patients; however, reproducible and accurate methods for identifying and segregating CTCs have remained a challenge. [7][8][9] Till date, epithelial cell surface markers are being used as a sole modality for isolation of rare population of CTCs by various systems. [10][11][12][13][14] Utilizing these markers for the effective isolation of CTCs may provide erroneous results as they result in the down-regulation of epithelial cell markers during the epithelial-mesenchymal transition (EMT).…”

Section: Introductionmentioning

confidence: 99%

Evidence for circulating cancer stem-like cells and epithelial–mesenchymal transition phenotype in the pleurospheres derived from lung adenocarcinoma using liquid biopsy

2017

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Lung cancer stem cells are supposed to be the main drivers of tumor initiation, maintenance, drug resistance, and relapse of the disease. Hence, identification of the cellular and molecular aspects of these cells is a prerequisite for targeted therapy of lung cancer. Currently, analysis of circulating tumor cells has the potential to become the main diagnostic technique to monitor disease progression or therapeutic response as it is non-invasive. However, accurate detection of circulating tumor cells has remained a challenge, as epithelial cell markers used so far are not always trustworthy for detecting circulating tumor cells, especially during epithelial-mesenchymal transition. As cancer stem cells are the only culprit to initiate metastatic tumors, our aim was to isolate and characterize circulating tumor stem cells rather than circulating tumor cells from the peripheral blood of NSCLC adenocarcinoma as limited data are available addressing the gene expression profiling of lung cancer stem cells. Here, we reveal that CD44(+)/CD24(−) population in circulation not only exhibit stem cell-related genes but also possess epithelial-mesenchymal transition characteristics. In conclusion, the use of one or more cancer stem cell markers along with epithelial, mesenchymal and epithelial mesenchymal transition markers will prospectively provide the most precise assessment of the threat for recurrence and metastatic disease and has a great potential for forthcoming applications in harvesting circulating tumor stem cells and their downstream applications. Our results will aid in developing diagnostic and prognostic modalities and personalized treatment regimens like dendritic cell-based immunotherapy that can be utilized for targeting and eliminating circulating tumor stem cells, to significantly reduce the possibility of relapse and improve clinical outcomes.

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Section: Introductionmentioning

confidence: 99%

Evidence for circulating cancer stem-like cells and epithelial–mesenchymal transition phenotype in the pleurospheres derived from lung adenocarcinoma using liquid biopsy

2017

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“…Technology for CTC isolation uses either physical separation or immunoaffinity-based methods for CTC enrichment. [9] Physical separation is based on their biophysical and biomechanical properties which distinguish CTCs from normal blood cells, e.g., size (larger; >8 μm), less deformability, density, and electricity. Immunoaffinity-based enrichment is based on a CTC marker usually a cell surface protein.…”

Section: Methods For Circulating Tumor Cells Isolation and Detectionmentioning

confidence: 99%

Circulating tumor cells in breast cancer

Jain¹,

Suryavanshi²,

Batra³

et al. 2017

Int J Mol Immuno Oncol.

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Breast cancer is a heterogeneous disease. Liquid biopsy is a novel diagnostic tool and may provide answers to many questions related to unevenness in prognosis and ultimate outcome. Different technologies for CTC isolation, enrichment, detection, and characterization are under evaluation. Various clinical trials and meta-analysis have been conducted to define the role of CTC in early and metastatic breast cancer. CTCs are superior to other serum markers for prognostication. Their role as predictive marker remains elusive.

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“…Some of these methods exploit physical differences in size, density, deformability or electrical properties between CTCs and blood cells (reviewed in [59]), (9,60). However, methods that rely on the assumption that CTCs are larger than nucleated blood cells are flawed, as tumor cells in different stages of the cell cycle, undergoing apoptosis, or in EMT may be smaller in size (59). In addition, the issue of CTC deformability is controversial, being difficult to characterize and lacking precision (61).…”

Section: New Techniques For Ctc Enrichment and Identificationmentioning

confidence: 99%

Detection and Clinical Significance of Circulating Tumor Cells in Colorectal Cancer—20 Years of Progress

Hardingham

Grover

Winter

et al. 2015

Mol Med

124

104

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Circulating tumor cells (CTC) may be defined as tumor-or metastasis-derived cells that are present in the bloodstream. The CTC pool in colorectal cancer (CRC) patients may include not only epithelial tumor cells, but also tumor cells undergoing epithelial-mesenchymal transition (EMT) and tumor stem cells. A significant number of patients diagnosed with early stage CRC subsequently relapse with recurrent or metastatic disease despite undergoing "curative" resection of their primary tumor. This suggests that an occult metastatic disease process was already underway, with viable tumor cells being shed from the primary tumor site, at least some of which have proliferative and metastatic potential and the ability to survive in the bloodstream. Such tumor cells are considered to be responsible for disease relapse in these patients. Their detection in peripheral blood at the time of diagnosis or after resection of the primary tumor may identify those early-stage patients who are at risk of developing recurrent or metastatic disease and who would benefit from adjuvant therapy. CTC may also be a useful adjunct to radiological assessment of tumor response to therapy. Over the last 20 years many approaches have been developed for the isolation and characterization of CTC. However, none of these methods can be considered the gold standard for detection of the entire pool of CTC. Recently our group has developed novel unbiased inertial microfluidics to enrich for CTC, followed by identification of CTC by imaging flow cytometry. Here, we provide a review of progress on CTC detection and clinical significance over the last 20 years.

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Circulating tumor cells: Advances in isolation and analysis, and challenges for clinical applications

Cited by 168 publications

References 145 publications

Evidence for circulating cancer stem-like cells and epithelial–mesenchymal transition phenotype in the pleurospheres derived from lung adenocarcinoma using liquid biopsy

Evidence for circulating cancer stem-like cells and epithelial–mesenchymal transition phenotype in the pleurospheres derived from lung adenocarcinoma using liquid biopsy

Circulating tumor cells in breast cancer

Detection and Clinical Significance of Circulating Tumor Cells in Colorectal Cancer—20 Years of Progress

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