Promise and limits of the CellSearch platform for evaluating pharmacodynamics in circulating tumor cells

Wang, Lihua; Balasubramanian, Priya; Chen, Alice; Kummar, Shivaani; Evrard, Yvonne A.; Kinders, Robert J.

doi:10.1053/j.seminoncol.2016.06.004

Cited by 106 publications

(83 citation statements)

References 36 publications

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“…The “needle in a haystack” paradigm was overcome with the improvements in isolation platforms, which have driven the field exponentially . With the advent of the FDA‐approved CellSearch system (Menarini Silicon Biosystems, Huntingdon Valley, PA), important clinical correlations repeatedly arose between CTC enumeration and survival parameters (overall survival, progression‐free survival) in several tumor types, such as breast, prostate, and colorectal cancers …”

Section: Introductionmentioning

confidence: 99%

The prognostic significance of circulating tumor cells in head and neck and non‐small‐cell lung cancer

et al. 2018

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Tumor biopsy is the gold standard for the assessment of clinical biomarkers for treatment. However, tumors change dynamically in response to therapy, and there remains a need for a more representative biomarker that can be assayed over the course of treatment. Circulating tumor cells (CTCs) may provide clinically important and comprehensive tumoral information that is predictive of treatment response and outcome. Blood samples were processed for CTCs from 56 patients using the ClearCell FX system. Captured cells were phenotyped for CTC clusters and markers for immunotherapy (PD‐L1) CTC chromosomal architecture (ALK, EGFR). CTCs were isolated in 11/23 (47.8%) of head and neck cancer (HNC) patients and 17/33 (51.5%) of non‐small‐cell lung cancer (NSCLC) patients. CTCs were determined to be PD‐L1‐positive in 6/11 (54.4%) HNC and 11/17 (64.7%) NSCLC cases, respectively. 3D chromosomal DNA FISH for ALK and EGFR molecular targets showed better resolution than in 2D when imaging CTCs. HNC CTC‐positive patients had shorter progression‐free survival (PFS) (hazard ratio[HR]: 4.946; 95% confidence internal[CI]:1.571‐15.57; P = 0.0063), and PD‐L1‐positive CTCs were found to be significantly associated with worse outcome ([HR]:5.159; 95% [CI]:1.011‐26.33; P = 0.0485). In the advanced stage NSCLC patient cohort, PFS was not found to be associated with CTCs prior to therapy ([HR]:2.246; 95% [CI]:0.9565‐5.273; P = 0.0632), nor the presence of PD‐L1 expression ([HR]:1.646; 95% [CI]:0.5128‐5.283; P = 0.4023). This study demonstrated that CTCs are predictive of poorer outcomes in HNC and provides distinct and separate utility for CTCs in HNC and NSCLC, which may be more representative of the disease burden and overall survival than the parameters used to measure them.

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Section: Introductionmentioning

confidence: 99%

The prognostic significance of circulating tumor cells in head and neck and non‐small‐cell lung cancer

et al. 2018

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“…Identification and isolation of CTCs in BC patients are usually based on the determination of surface epithelial markers, particularly EpCAM and cytokeratins (CK8, CK18, and CK19), and the exclusion of leukocytes by using CD45 [34][35][36]. N-cadherin, vimentin, Twist, Snail, Zeb, and other markers are used for counting CTCs in the EMT state [5].…”

Section: Ctc Heterogeneity and The Molecular Makeup Of Metastatic Cellsmentioning

confidence: 99%

“…Moreover, CTCs are not detected in most of the patients, and when detected, the number of CTCs is usually low-< 5 cells per 7.5 mL [33]. Conclusions on CTC heterogeneity are mostly obtained from patients with the largest numbers of CTCs, which probably have the most aggressive tumors [34].Identification and isolation of CTCs in BC patients are usually based on the determination of surface epithelial markers, particularly EpCAM and cytokeratins (CK8, CK18, and CK19), and the exclusion of leukocytes by using CD45 [34][35][36]. N-cadherin, vimentin, Twist, Snail, Zeb, and other markers are used for counting CTCs in the EMT state [5].…”

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confidence: 99%

Heterogeneity of Circulating Tumor Cells in Breast Cancer: Identifying Metastatic Seeds

Menyailo

Tretyakova

Denisov

2020

IJMS

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Metastasis being the main cause of breast cancer (BC) mortality represents the complex and multistage process. The entrance of tumor cells into the blood vessels and the appearance of circulating tumor cells (CTCs) seeding and colonizing distant tissues and organs are one of the key stages in the metastatic cascade. Like the primary tumor, CTCs are extremely heterogeneous and presented by clusters and individual cells which consist of phenotypically and genetically distinct subpopulations. However, among this diversity, only a small number of CTCs is able to survive in the bloodstream and to form metastases. The identification of the metastasis-initiating CTCs is believed to be a critical issue in developing therapeutic strategies against metastatic disease. In this review, we summarize the available literature addressing morphological, phenotypic and genetic heterogeneity of CTCs and the molecular makeup of specific subpopulations associated with BC metastasis. Special attention is paid to the need for in vitro and in vivo studies to confirm the tumorigenic and metastatic potential of metastasis-associating CTCs. Finally, we consider treatment approaches that could be effective to eradicate metastatic CTCs and to prevent metastasis. with partial EMT) and high metastatic potential [18,19]. In addition to the EMT features, CTCs can also exhibit stem-like characteristics, particularly self-renewal and multilineage differentiation ability [20].There is still no highly effective therapy for metastatic BC. Therapy targeted directly against CTCs seems to be promising. To date, various molecular markers of CTCs and their therapeutic targets that can be used to prevent cancer progression are known [21]. In addition, different therapeutic approaches for the elimination of CTCs have been proposed; however, none of them has been clinically approved. The reason is that the molecular and biological characteristics of the primary tumor and CTCs are not well understood. In our opinion, the main focus should be on the search for specific populations of CTCs responsible for the development of metastasis and the study of their molecular makeup. These cells could be the primary therapeutic target for preventing metastatic progression [22]. Recent advances in single-cell sequencing allow one to determine the population structure of CTCs and identify metastasis-initiating cells [23][24][25][26], while in vitro and in vivo studies provide data on their proliferative, apoptotic, invasive, and other phenotypes [27].Nowadays, despite a large number of studies on CTC heterogeneity and their metastatic potential, there are still no generally accepted and universal markers of CTCs prone to metastasis. In this review, we systematized the data on metastatic CTCs in terms of their morphological, phenotypic, and genetic heterogeneity in BC, as well as emphasized the importance of studying these cells in vitro and in vivo and developing therapeutic approaches for their elimination to prevent metastasis. CTC Heterogeneity and the Molecular Makeup...

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“…Specifically, this technology allowed for CTC enumeration across a broad variety of epithelial cancers. [ 7 ] The observation that tumor cells overexpress EpCAM has been employed to detect these cells from peripheral blood samples with other approaches as well, including immunocytochemistry, [ 8 ] enzyme‐linked immunosorbent spot (ELISPOT) assays, [ 9 ] and “CellSpotter” systems. [ 10 ] For most of these methods, lack of data reproducibility has hindered their widespread adoption, and CellSearch is the only one that has been clinically validated and Food and Drug Administration (FDA)‐cleared for enumeration of CTCs in human blood.…”

Section: Introductionmentioning

confidence: 99%

Exploring Circulating Tumor Cells in Cholangiocarcinoma Using a Novel Glycosaminoglycan Probe on a Microfluidic Platform

Gopinathan

Chiang

Bandaru

et al. 2020

Adv Healthcare Materials

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The search of alternative approaches to epithelial cell adhesion molecule (EpCAM), for the isolation of circulating tumor cells (CTC), is on the rise. This work attempts at evaluating the feasibility of using a new glycosaminoglycan, SCH45, as a probe to isolate CTCs from the peripheral blood of 65 advanced/metastatic cholangiocarcinoma (CCA) patients. The positive enrichment of CTCs from 1 mL of blood using SCH45‐bound magnetic beads and subsequent staining on an integrated microfluidic platform is demonstrated. Results detailing CTC concentrations averaging ≥1 CTCs mL−1 of blood are shown, and a conventional protein biomarker, EpCAM, has been used to corroborate the finding that 100% of the patients possess CTCs in their blood. Studies detailing the use of CTCs in the prognostic monitoring and treatment effectiveness of advanced/metastatic CCA are scarce, and the isolation of CTCs from all CCA patients tested has not been reported yet. A strong correlation between CTC counts and disease progression at the time of and/or in advance of radiographic imaging in patients receiving chemotherapy is also reported. This study is one of its kind with the new probe and reduced sample volume and has potential for use in CCA diagnosis and prognosis in the near future.

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Promise and limits of the CellSearch platform for evaluating pharmacodynamics in circulating tumor cells

Cited by 106 publications

References 36 publications

The prognostic significance of circulating tumor cells in head and neck and non‐small‐cell lung cancer

The prognostic significance of circulating tumor cells in head and neck and non‐small‐cell lung cancer

Heterogeneity of Circulating Tumor Cells in Breast Cancer: Identifying Metastatic Seeds

Exploring Circulating Tumor Cells in Cholangiocarcinoma Using a Novel Glycosaminoglycan Probe on a Microfluidic Platform

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