Characterization of circulating tumor cell aggregates identified in patients with epithelial tumors

Cho, Edward H.; Wendel, Marco; Luttgen, Madelyn; Yoshioka, Craig; Marrinucci, Dena; Lazar, Daniel C.; Schram, Ethan; Nieva, Jorgé; Bazhenova, Lyudmila; Morgan, Alison; Ko, Andrew H.; Korn, W. Michael; Kolatkar, Anand; Bethel, Kelly; Kühn, Peter

doi:10.1088/1478-3975/9/1/016001

Cited by 179 publications

(149 citation statements)

References 13 publications

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“…Consistent with the detection of tumor emboli in clinical specimens, tumor cell clusters in the blood have been observed using various technologies in cancers of the breast, pancreas, kidney, colon, lung, and melanoma [3,5, 10,44,[61][62][63][64]. The presence of CTC clusters in the blood has also been associated with a poor prognosis in patients with lung, breast, or prostate cancers [65][66][67].…”

Section: Studies Of Ctc Clusters In Circulationmentioning

confidence: 63%

En Route to Metastasis: Circulating Tumor Cell Clusters and Epithelial-to-Mesenchymal Transition

et al. 2015

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Section: Studies Of Ctc Clusters In Circulationmentioning

confidence: 63%

En Route to Metastasis: Circulating Tumor Cell Clusters and Epithelial-to-Mesenchymal Transition

et al. 2015

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“…The HD-CTC assay was shown to be feasible in identifying and characterizing CTC aggregates, and found to occur often in patients with metastatic breast, NSCLC, pancreatic, and prostate cancer (42). Subsequent mouse models have shown that CTC clusters arise from oligoclonal tumor cell groups rather than aggregation intravascularly, and these cluster are important mediators of cancer metastases (43).…”

Section: Hd-ctcmentioning

confidence: 99%

Biophysical technologies for understanding circulating tumor cell biology and metastasis

Nieva

2017

Transl. Lung Cancer Res.

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An understanding of cancer evolution in lung cancer with its associated resistance to therapy can only be achieved with repeated sampling and analysis of the cancer. Given the high risks and costs associated with repeat physical biopsy, alternative technologies must be applied. Several modalities exist for analysis and re-analysis of cancer biology. Among them are the CellSearch platform, the CTC chip, and the highdefinition CTC platform. While the former is primarily able to provide prognosticating information in the form of CTC enumeration, the latter two have the advantage of serving as a platform to study tumor biology. Techniques for analysis of single cell genomics, as well as protein expression on a single cell basis provide scientists with the capacity to understand cancer cell populations as a collection of individual cells, rather than as an average of all cells. A multimodal combination of circulating tumor DNAs (ctDNAs), CTCs, proteomics, and CTC-derived xenografts (CDXs) to create computational models useful in diagnosis, prognostication, and predictiveness to treatment is likely the future of tailoring individualized cancer care.

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“…Another unbiased, label-free approach has been developed by Epic Sciences (CA, USA) in which CTCs undergo no enrichment other than erythrocyte lysis, are plated on multiple slides, and then identified against a background of excess leukocytes by high-throughput immunofluorescence microscopy [78][79][80] (Figure 1). This platform was recently used by Scher and colleagues to demonstrate that CTC expression of AR-V7 in patients with metastatic castrate-resistant prostate cancer is associated with longer survival on taxane chemotherapy as opposed to AR-targeted therapies [81].…”

Section: High-throughput Microscopymentioning

confidence: 99%

The Promise of Circulating Tumor Cells for Precision Cancer Therapy

Hwang

Miyamoto

2016

Biomark. Med.

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The rapidly growing array of therapeutic options in cancer requires informative biomarkers to guide the rational selection and precision application of appropriate therapies. Circulating biomarkers such as circulating tumor cells have immense potential as noninvasive, serial 'liquid biopsies' that may be more representative of the complete spectrum of a patient's individual malignancy than spatially and temporally restricted tumor biopsies. In this review, we discuss the current state-of-the-art in the isolation and molecular characterization of circulating tumor cells as well as their utility in a wide range of clinical applications such as prognostics, treatment monitoring and identification of novel therapeutic targets and resistance mechanisms to enable real-time adjustments in the clinical management of cancer. The evolving landscape of cancer therapy creates an urgent need for minimally invasive biomarkers to facilitate early detection, prognosis and prediction of therapeutic response and resistance to enable highly adaptable, real-time precision therapy [1]. The conventional gold standard of using single biopsies of the primary tumor to inform all downstream therapeutic decisions may no longer be adequate given increasing evidence of significant spatial and temporal hetero geneity in tumors [2], especially when placed under the selection pressure of various treatments. Moreover, serial biopsies are often impractical, morbid and technically challenging.In this review, we focus on the emerging role of circulating tumor cells (CTCs), which can be serially obtained from minimally invasive blood draws or 'liquid biopsies'. CTCs are cancer cells that have been shed into the peripheral circulation from primary or metastatic tumors [3,4]. The first reported observation of CTCs was in 1869 by Australian pathologist Thomas Ashworth at the autopsy of a patient with metastatic cancer [5]. By comparing the morphology of circulating cells with those from different cancerous lesions, Ashworth came to the prescient conclusion that 'cells identical with those of the cancer itself being seen in the blood may tend to throw some light upon the mode of origin of multiple tumors existing in the same person' [5]. Indeed, molecular analyses of CTCs may be superior to individual tumor biopsies because these circulating cells likely provide a sampling of different regions of the primary tumor as well as metastatic deposits, and therefore are more likely to capture the genetic heterogeneity of a patient's cancer.While cell-free circulating tumor DNA (ctDNA) is an important, complementary biomarker to CTCs, it has been reviewed extensively elsewhere and will not be discussed in this review [4,6]. Moreover, although ctDNA may in some cases be more reliably [7], they are largely limited to genomic mutational analysis. In contrast, CTC analysis can provide a wealth of other information including cell morphology, immunocytochemical phenotype, presence of important epitopes, presence of multiple mutations within a single cell to decode ...

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Characterization of circulating tumor cell aggregates identified in patients with epithelial tumors

Cited by 179 publications

References 13 publications

En Route to Metastasis: Circulating Tumor Cell Clusters and Epithelial-to-Mesenchymal Transition

En Route to Metastasis: Circulating Tumor Cell Clusters and Epithelial-to-Mesenchymal Transition

Biophysical technologies for understanding circulating tumor cell biology and metastasis

The Promise of Circulating Tumor Cells for Precision Cancer Therapy

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