Circulating Tumor Cells: Diagnostic and Therapeutic Applications

2018 ◽  
Vol 20 (1) ◽  
pp. 329-352 ◽  
Author(s):  
Eric Lin ◽  
Thong Cao ◽  
Sunitha Nagrath ◽  
Michael R. King
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Poor Prognosis ◽  
Experimental Therapeutics ◽  
Next Generation ◽  
Therapeutic Applications

Metastasis contributes to poor prognosis in many types of cancer and is the leading cause of cancer-related deaths. Tumor cells metastasize to distant sites via the circulatory and lymphatic systems. In this review, we discuss the potential of circulating tumor cells for diagnosis and describe the experimental therapeutics that aim to target these disseminating cancer cells. We discuss the advantages and limitations of such strategies and how they may lead to the development of the next generation of antimetastasis treatments.

scholarly journals The Mechanical Fingerprint of Circulating Tumor Cells (CTCs) in Breast Cancer Patients

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1119
Author(s):  
Ivonne Nel ◽  
Erik W. Morawetz ◽  
Dimitrij Tschodu ◽  
Josef A. Käs ◽  
Bahriye Aktas
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Hematopoietic Cells ◽  
Surrogate Marker ◽  
Clinical Samples ◽  
Breast Cancer Patients ◽  
Shape Restoration

Circulating tumor cells (CTCs) are a potential predictive surrogate marker for disease monitoring. Due to the sparse knowledge about their phenotype and its changes during cancer progression and treatment response, CTC isolation remains challenging. Here we focused on the mechanical characterization of circulating non-hematopoietic cells from breast cancer patients to evaluate its utility for CTC detection. For proof of premise, we used healthy peripheral blood mononuclear cells (PBMCs), human MDA-MB 231 breast cancer cells and human HL-60 leukemia cells to create a CTC model system. For translational experiments CD45 negative cells—possible CTCs—were isolated from blood samples of patients with mamma carcinoma. Cells were mechanically characterized in the optical stretcher (OS). Active and passive cell mechanical data were related with physiological descriptors by a random forest (RF) classifier to identify cell type specific properties. Cancer cells were well distinguishable from PBMC in cell line tests. Analysis of clinical samples revealed that in PBMC the elliptic deformation was significantly increased compared to non-hematopoietic cells. Interestingly, non-hematopoietic cells showed significantly higher shape restoration. Based on Kelvin–Voigt modeling, the RF algorithm revealed that elliptic deformation and shape restoration were crucial parameters and that the OS discriminated non-hematopoietic cells from PBMC with an accuracy of 0.69, a sensitivity of 0.74, and specificity of 0.63. The CD45 negative cell population in the blood of breast cancer patients is mechanically distinguishable from healthy PBMC. Together with cell morphology, the mechanical fingerprint might be an appropriate tool for marker-free CTC detection.

A Microfluidic Platform for On-Chip Analysis of Circulating Tumor Cells

2021 ◽  
Author(s):  
Jeff Darabi ◽  
Joseph Schober
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Whole Blood ◽  
Peripheral Blood ◽  
Automated Image Analysis ◽  
Rare Cancer ◽  
On Chip ◽  
Chip Analysis ◽  
Selection Of

Abstract Studies have shown that primary tumor sites begin shedding cancerous cells into peripheral blood at early stages of cancer, and the presence and frequency of circulating tumor cells (CTCs) in blood is directly proportional to disease progression. The challenge is that the concentration of the CTCs in peripheral blood may be extremely low. In the past few years, several microfluidic-based concepts have been investigated to isolate CTCs from whole blood. However, these devices are generally hampered by complex fabrication processes and very low volumetric throughputs, which may not be practical for rapid clinical applications. This paper presents a high-performance yet simple magnetophoretic microfluidic chip for the enrichment and on-chip analysis of rare CTCs from blood. Microscopic and flow cytometric assays developed for selection of cancer cell lines, selection of monoclonal antibodies, and optimization of bead coupling are discussed. Additionally, on-chip characterization of rare cancer cells using high resolution immunofluorescence microscopy and modeling results for prediction of CTC capture length are presented. The device has the ability to interface directly with on-chip pre and post processing modules such as mixing, incubation, and automated image analysis systems. These features will enable us to isolate rare cancer cells from whole blood and detect them on the chip with subcellular resolution.

scholarly journals Circulating tumor cells: a valuable marker of poor prognosis for advanced nasopharyngeal carcinoma

2019 ◽  
Vol 25 (1) ◽  
Author(s):  
Guoping Ou ◽  
Shan Xing ◽  
Jianpei Li ◽  
Lin Zhang ◽  
Shulin Chen
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Roc Curve ◽  
Poor Prognosis ◽  
Regression Models ◽  
Prognostic Value ◽  
Stage Iv ◽  
Stage Iii ◽  
Ebv Dna

Abstract Purpose To evaluate the prognostic value of circulating tumor cells (CTCs) in nasopharyngeal carcinoma (NPC). Methods Cox’s proportional hazards regression models were used to identify whether CTCs was a poor prognostic factor for NPC. Chi-square tests were used to analyze and compare the distribution characteristics of CTCs in NPC. ROC curve was used to estimate the cut-off point of CTCs. Kaplan-Meier survival analyses were used to observe the prognostic value of CTCs alone and in combined with Epstein-Barr Virus DNA (EBV-DNA). Results CTCs was confirmed to be an independent risk factor for poor prognosis of NPC by Cox’s regression models that enrolled 370 NPC cases and took age, gender, EBV-DNA and CTCs as variables. The proportion of CTCs in stage IV NPC was statistically different from that in stage III; the cut-off point of CTCs between stage IV (288 cases) and stage III (70 cases) NPC estimated by ROC curve was 0.5. The prognosis of advanced NPC patients became worse with the increase of CTCs count. The combined detection of CTCs and EBV-DNA could better predict the prognosis of NPC compared with the single detection of EBV-DNA.

Continuously capturing circulating cancer cells

2019 ◽  
Vol 11 (489) ◽  
pp. eaax1730
Author(s):  
Rajan P. Kulkarni
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Circulating Cancer Cells

A wearable apheresis device allows for continuous and specific capture of circulating tumor cells.

scholarly journals Mass Action Kinetic Model of Apoptosis by TRAIL-Functionalized Leukocytes

2018 ◽  
Author(s):  
Emily E. Lederman ◽  
Michael R. King
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Prolonged Exposure ◽  
Mass Action ◽  
New Approach ◽  
Membrane Bound ◽  
Soluble Trail ◽  
Kinetics Of ◽  
Coupled Reaction

1 AbstractBackgroundMetastasis through the bloodstream contributes to poor prognosis in many types of cancer. A unique approach to target and kill colon, prostate, and other epithelial-type cancer cells in the blood has been recently developed that causes circulating leukocytes to present the cancer-specific, liposome-bound Tumor Necrosis Factor (TNF)-related apoptosis inducing ligand (TRAIL) on their surface along with E – selectin adhesion receptors. This approach, demonstrated both in vitro with human blood and in mice, mimics the cytotoxic activity of natural killer cells. The resulting liposomal TRAIL-coated leukocytes hold promise as an effective means to neutralize circulating tumor cells that enter the bloodstream with the potential to form new metastases.ResultsThe computational biology study reported here examines the mechanism of this effective signal delivery, by considering the kinetics of the coupled reaction cascade, from TRAIL binding death receptor to eventual apoptosis. In this study, a collision of bound TRAIL with circulating tumor cells (CTCs) is considered and compared to a prolonged exposure of CTCs to soluble TRAIL. An existing computational model of soluble TRAIL treatment was modified to represent the kinetics from a diffusion-limited 3D reference frame into a 2D collision frame with advection and adhesion to mimic the E – selectin and membrane bound TRAIL treatment. Thus, the current model recreates the new approach of targeting cancer cells within the blood. The model was found to faithfully reproduce representative observations from experiments of liposomal TRAIL treatment under shear. The model predicts apoptosis of CTCs within 2 hr when treated with membrane bound TRAIL, while apoptosis in CTCs treated with soluble TRAIL proceeds much more slowly over the course of 10 hrs, consistent with previous experiments. Given the clearance rate of soluble TRAIL in vivo, this model predicts that the soluble TRAIL method would be rendered ineffective, as found in previous experiments.ConclusionThis study therefore indicates that the kinetics of the coupled reaction cascade of liposomal E – selectin and membrane bound TRAIL colliding with CTCs can explain why this new approach to target and kill cancer cells in blood is much more effective than its soluble counterpart.

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