scholarly journals Circulating Tumor Cells: Technologies and Their Clinical Potential in Cancer Metastasis

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1111
Author(s):  
Jerry Xiao ◽  
Paula R. Pohlmann ◽  
Claudine Isaacs ◽  
Benjamin A. Weinberg ◽  
Aiwu R. He ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Metastasis ◽  
Immune Cell ◽  
Single Cells ◽  
Circulatory System ◽  
Clinical Importance ◽  
Progression Free Survival ◽  
Primary Tumors ◽  
Isolation Techniques

Circulating tumor cells (CTCs) are single cells or clusters of cells within the circulatory system of a cancer patient. While most CTCs will perish, a small proportion will proceed to colonize the metastatic niche. The clinical importance of CTCs was reaffirmed by the 2008 FDA approval of CellSearch®, a platform that could extract EpCAM-positive, CD45-negative cells from whole blood samples. Many further studies have demonstrated the presence of CTCs to stratify patients based on overall and progression-free survival, among other clinical indices. Given their unique role in metastasis, CTCs could also offer a glimpse into the genetic drivers of metastasis. Investigation of CTCs has already led to groundbreaking discoveries such as receptor switching between primary tumors and metastatic nodules in breast cancer, which could greatly affect disease management, as well as CTC-immune cell interactions that enhance colonization. In this review, we will highlight the growing variety of isolation techniques for investigating CTCs. Next, we will provide clinically relevant context for CTCs, discussing key clinical trials involving CTCs. Finally, we will provide insight into the future of CTC studies and some questions that CTCs are primed to answer.

scholarly journals Nanotechnology-Assisted Isolation and Analysis of Circulating Tumor Cells on Microfluidic Devices

Micromachines ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 774 ◽  
Author(s):  
Jie Cheng ◽  
Yang Liu ◽  
Yang Zhao ◽  
Lina Zhang ◽  
Lingqian Zhang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Liquid Biopsy ◽  
Cancer Metastasis ◽  
Human Peripheral Blood ◽  
Microfluidic Devices ◽  
Detection Sensitivity ◽  
Cell Capture ◽  
Primary Tumors ◽  
Downstream Analysis

Circulating tumor cells (CTCs), a type of cancer cell that spreads from primary tumors into human peripheral blood and are considered as a new biomarker of cancer liquid biopsy. It provides the direction for understanding the biology of cancer metastasis and progression. Isolation and analysis of CTCs offer the possibility for early cancer detection and dynamic prognosis monitoring. The extremely low quantity and high heterogeneity of CTCs are the major challenges for the application of CTCs in liquid biopsy. There have been significant research endeavors to develop efficient and reliable approaches to CTC isolation and analysis in the past few decades. With the advancement of microfabrication and nanomaterials, a variety of approaches have now emerged for CTC isolation and analysis on microfluidic platforms combined with nanotechnology. These new approaches show advantages in terms of cell capture efficiency, purity, detection sensitivity and specificity. This review focuses on recent progress in the field of nanotechnology-assisted microfluidics for CTC isolation and detection. Firstly, CTC isolation approaches using nanomaterial-based microfluidic devices are summarized and discussed. The different strategies for CTC release from the devices are specifically outlined. In addition, existing nanotechnology-assisted methods for CTC downstream analysis are summarized. Some perspectives are discussed on the challenges of current methods for CTC studies and promising research directions.

scholarly journals Relevance of Circulating Tumor Cells as Predictive Markers for Cancer Incidence and Relapse

2022 ◽  
Vol 15 (1) ◽  
pp. 75
Author(s):  
Chaithanya Chelakkot ◽  
Hobin Yang ◽  
Young Kee Shin
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Progression ◽  
Cancer Incidence ◽  
Single Cells ◽  
Circulatory System ◽  
Predictive Marker ◽  
Response To Therapy ◽  
Cancer Prognosis ◽  
Novel Technologies

Shedding of cancer cells from the primary site or undetectable bone marrow region into the circulatory system, resulting in clinically overt metastasis or dissemination, is the hallmark of unfavorable invasive cancers. The shed cells remain in circulation until they extravasate to form a secondary metastatic lesion or undergo anoikis. The circulating tumor cells (CTCs) found as single cells or clusters carry a plethora of information, are acknowledged as potential biomarkers for predicting cancer prognosis and cancer progression, and are supposed to play key roles in determining tailored therapies for advanced diseases. With the advent of novel technologies that allow the precise isolation of CTCs, more and more clinical trials are focusing on the prognostic and predictive potential of CTCs. In this review, we summarize the role of CTCs as a predictive marker for cancer incidence, relapse, and response to therapy.

scholarly journals High blood flow shear stress values are associated with circulating tumor cells cluster disaggregation in a multi-channel microfluidic device

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245536
Author(s):  
Alessandra Marrella ◽  
Arianna Fedi ◽  
Gabriele Varani ◽  
Ivan Vaccari ◽  
Marco Fato ◽  
...  
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Microfluidic Device ◽  
Single Cells ◽  
Biological Significance ◽  
Circulatory System ◽  
Cfd Modeling

Metastasis represents a dynamic succession of events involving tumor cells which disseminate through the organism via the bloodstream. Circulating tumor cells (CTCs) can flow the bloodstream as single cells or as multicellular aggregates (clusters), which present a different potential to metastasize. The effects of the bloodstream-related physical constraints, such as hemodynamic wall shear stress (WSS), on CTC clusters are still unclear. Therefore, we developed, upon theoretical and CFD modeling, a new multichannel microfluidic device able to simultaneously reproduce different WSS characterizing the human circulatory system, where to analyze the correlation between SS and CTC clusters behavior. Three physiological WSS levels (i.e. 2, 5, 20 dyn/cm2) were generated, reproducing values typical of capillaries, veins and arteries. As first validation, triple-negative breast cancer cells (MDA-MB-231) were injected as single CTCs showing that higher values of WSS are correlated with a decreased viability. Next, the SS-mediated disaggregation of CTC clusters was computationally investigated in a vessels-mimicking domain. Finally, CTC clusters were injected within the three different circuits and subjected to the three different WSS, revealing that increasing WSS levels are associated with a raising clusters disaggregation after 6 hours of circulation. These results suggest that our device may represent a valid in vitro tool to carry out systematic studies on the biological significance of blood flow mechanical forces and eventually to promote new strategies for anticancer therapy.

sVEGFR2 and circulating tumor cells to predict for the efficacy of pazopanib in neuroendocrine tumors (NETs): PAZONET subgroup analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4140-4140 ◽  
Author(s):  
Enrique Grande ◽  
Oriol Casanovas ◽  
Julie Earl ◽  
Daniel E. Castellano ◽  
Rocio Garcia-Carbonero ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Predictive Biomarkers ◽  
Progression Free Survival ◽  
Somatostatin Analogues ◽  
Tumor Location ◽  
Circulating Endothelial Cells ◽  
Duration Of Treatment ◽  
Primary Tumors ◽  
Free Survival

4140 Background: The PAZONET trial (Grande et al, ESMO 2012) performed by the GETNE group analyzed the efficacy and safety of the use of pazopanib (800 mg/qd) in patients (pts) with progressive metastatic NETs that had been previously treated with other novel targeted agents. Here we report on the relationship between clinical outcome and circulating and tumor-related biomarkers. Methods: Kaplan-Meier analysis was used to correlate progression-free survival (PFS) with: blood circulating markers at baseline and after 12 weeks of treatment (VEGF-A and sVEGFR2 circulating plasma, Circulating Tumor Cells (CTC) and Circulating Endothelial Cells (CEC)), tumor functional status, Ki67, concomitant somatostatin analogues (SSA), chromogranin A (CgA) and primary tumor location. Results: 44 pts were enrolled, 42 were evaluable for response. sVEGFR2 decreased after 12 weeks of treatment (median decrease 20%, p<0.0001) and the duration of treatment with pazopanib was associated with a decrease in sVEGFR2 (p=0.0046). Pts with a decrease in sVEGFR2 of >20% and <=20% had a median progression-free survival (mPFS) of 12.6 and 9.1 months (mo) respectively (p=0.067). Pts with and without CTC at baseline had a mPFS of 5.8 and 9.1 mo respectively (p=0.12). VEGFA and CEC were not found to predict PFS. mPFS in the intention to treat population was 10.0 mo (95% CI 4.3-15.6). Significant differences in mPFS were found in concomitant SSA treatment (11.9 mo [10.6-13.2]) vs. pazopanib alone (4.8 mo [3.0-6.6]) (p=0.007); decrease of CgA (3.4 mo [0.0-6.8]) vs no decrease (11.2 mo [8.4-14.1]) (p=0.024) and pancreatic (12.8 mo [11.0-14.6]) vs gastrointestinal (10.0 mo [4.9-15.1]) vs other primary tumors (3.4 mo [0.0-7.0]). No differences in mPFS were seen in functioning (10.0 mo) and non-functioning tumors (9.3 mo) and Ki67 status (< 2% 10.0 mo, 3-10% 10.8 mo or >10% 4.1 mo). Conclusions: sVEGFR2 and baseline CTC are promising predictive biomarkers for pazopanib in NETs. The updated results confirm the efficacy of pazopanib as a sequencing treatment of pts with progressive NETs, particularly in those with pancreatic primary tumors. The combination of pazopanib and SSA seems to be synergistic. Clinical trial information: NCT01280201.

scholarly journals Dangerous Liaisons: Circulating Tumor Cells (CTCs) and Cancer-Associated Fibroblasts (CAFs)

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2861
Author(s):  
Pablo Hurtado ◽  
Inés Martínez-Pena ◽  
Roberto Piñeiro
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Metastasis ◽  
Current Knowledge ◽  
Single Cells ◽  
Metastatic Potential ◽  
Cancer Associated Fibroblasts ◽  
Cytokines And Chemokines ◽  
Paracrine Secretion ◽  
Cellular Components

The crosstalk between cancer cells and the tumor microenvironment (TME) is a key determinant of cancer metastasis. Cancer-associated fibroblasts (CAFs), one of the main cellular components of TME, promote cancer cell invasion and dissemination through mechanisms including cell-cell interactions and the paracrine secretion of growth factors, cytokines and chemokines. During metastasis, circulating tumor cells (CTCs) are shed from the primary tumor to the bloodstream, where they can be detected as single cells or clusters. The current knowledge about the biology of CTC clusters positions them as key actors in metastasis formation. It also indicates that CTCs do not act alone and that they may be aided by stromal and immune cells, which seem to shape their metastatic potential. Among these cells, CAFs are found associated with CTCs in heterotypic CTC clusters, and their presence seems to increase their metastatic efficiency. In this review, we summarize the current knowledge on the role that CAFs play on metastasis and we discuss their implication on the biogenesis, metastasis-initiating capacity of CTC clusters, and clinical implications. Moreover, we speculate about possible therapeutic strategies aimed to limit the metastatic potential of CTC clusters involving the targeting of CAFs as well as their difficulties and limitations.

scholarly journals ctcRbase: the gene expression database of circulating tumor cells and microemboli

Database ◽  
2020 ◽  
Vol 2020 ◽  
Author(s):  
Lei Zhao ◽  
Xiaohong Wu ◽  
Tong Li ◽  
Jian Luo ◽  
Dong Dong
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Metastasis ◽  
Circulating Tumor Cell ◽  
Gene Signature ◽  
Primary Tumors ◽  
A Genome ◽  
Experimental Validations ◽  
Transcriptomic Changes

Abstract Circulating tumor cells/microemboli (CTCs/CTMs) are malignant cells that depart from cancerous lesions and shed into the bloodstream. Analysis of CTCs can allow the investigation of tumor cell biomarker expression from a non-invasive liquid biopsy. To date, high-throughput technologies have become a powerful tool to provide a genome-wide view of transcriptomic changes associated with CTCs/CTMs. These data provided us much information to understand the tumor heterogeneity, and the underlying molecular mechanism of tumor metastases. Unfortunately, these data have been deposited into various repositories, and a uniform resource for the cancer metastasis is still unavailable. To this end, we integrated previously published transcriptome datasets of CTCs/CTMs and constructed a web-accessible database. The first release of ctcRbase contains 526 CTCs/CTM samples across seven cancer types. The expression of 14 631 mRNAs and 3642 long non-coding RNAs of CTCs/CTMs were included. Experimental validations from the published literature are also included. Since CTCs/CTMs are considered to be precursors of metastases, ctcRbase also collected the expression data of primary tumors and metastases, which allows user to discover a unique ‘circulating tumor cell gene signature’ that is distinct from primary tumor and metastases. An easy-to-use database was constructed to query and browse CTCs/CTMs genes. ctcRbase can be freely accessible at http://www.origin-gene.cn/database/ctcRbase/.

scholarly journals Lymph-Circulating Tumor Cells show distinct properties to Blood-Circulating Tumor Cells and constitute extraordinary efficient metastatic precursors

2018 ◽  
Author(s):  
Sulma I Mohammed ◽  
Odalys Torres Luquis ◽  
El Wood Walls ◽  
Frank Lloyd
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Primary Tumor ◽  
Cancer Metastasis ◽  
Expression Profiles ◽  
Parental Cell ◽  
Breast Cancer Metastasis ◽  
Primary Tumors ◽  
Gene And Protein Expression ◽  
Protein Expression Profiles

The molecular properties of tumor cells as they exit the primary tumor into the afferent lymphatics en route to the sentinel lymph nodes (SLNs) are not yet known. We developed an innovative technique that enables the collection of lymph and lymph-circulating tumor cells (LCTCs) en route to the SLN in immunocompetent animal model of breast cancer metastasis. We found that LCTCs and blood circulating tumor cells (BCTCs) as exited the primary tumor shared similar gene and protein expression profiles that were distinct from those of primary tumors and lymph node metastases (LNMs) despite their common parental cell origin. LCTCs but not BCTC exist in clusters, display a hybrid epithelial/mesenchymal phenotype and cancer stem cell-like properties and constitute extraordinarily efficient metastatic precursors. These results demonstrate that tumor cell metastasizing through the lymphatic are different from those spread by the blood circulation. The contribution of these cells to overall peripheral blood CTC is important in cancer therapy. Whether these two types of cells occur in cancer patients remain to be determined.

scholarly journals FlowCell-enriched circulating tumor cells as a predictor of lung cancer metastasis

Human Cell ◽  
2021 ◽  
Author(s):  
Yan Lu ◽  
Yushuang Zheng ◽  
Yuhong Wang ◽  
Dongmei Gu ◽  
Jun Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Metastasis ◽  
Lung Tumor ◽  
Early Stage ◽  
High Rate ◽  
Early Stage Lung Cancer ◽  
Lung Cancer Metastasis ◽  
Number Of Patients

AbstractLung cancer is the most fetal malignancy due to the high rate of metastasis and recurrence after treatment. A considerable number of patients with early-stage lung cancer relapse due to overlooked distant metastasis. Circulating tumor cells (CTCs) are tumor cells in blood circulation that originated from primary or metastatic sites, and it has been shown that CTCs are critical for metastasis and prognosis in various type of cancers. Here, we employed novel method to capture, isolate and classify CTC with FlowCell system and analyzed the CTCs from a cohort of 302 individuals. Our results illustrated that FlowCell-enriched CTCs effectively differentiated benign and malignant lung tumor and the total CTC counts increased as the tumor developed. More importantly, we showed that CTCs displayed superior sensitivity and specificity to predict lung cancer metastasis in comparison to conventional circulating biomarkers. Taken together, our data suggested CTCs can be used to assist the diagnosis of lung cancer as well as predict lung cancer metastasis. These findings provide an alternative means to screen early-stage metastasis.

scholarly journals Prognostic Threshold for Circulating Tumor Cells in Patients With Pancreatic and Midgut Neuroendocrine Tumors

2020 ◽  
Author(s):  
Dalvinder Mandair ◽  
Mohid S Khan ◽  
Andre Lopes ◽  
Luke Furtado O’Mahony ◽  
Leah Ensell ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Neuroendocrine Tumors ◽  
Operating Characteristic ◽  
Characteristic Curve ◽  
Multivariate Logistic Regression Analysis ◽  
Progression Free Survival ◽  
Free Survival ◽  
Optimum Threshold

Abstract Background Circulating tumor cells (CTCs) are detectable in patients with neuroendocrine tumors (NETs) and are accurate prognostic markers although the optimum threshold has not been defined. Objective This work aims to define optimal prognostic CTC thresholds in PanNET and midgut NETs. Patients and Methods CellSearch was used to enumerate CTCs in 199 patients with metastatic pancreatic (PanNET) (90) or midgut NETs (109). Patients were followed for progression-free survival (PFS) and overall survival (OS) for a minimum of 3 years or until death. Results The area under the receiver operating characteristic curve (AUROC) for progression at 12 months in PanNETs and midgut NETs identified the optimal CTC threshold as 1 or greater and 2 or greater, respectively. In multivariate logistic regression analysis, these thresholds were predictive for 12-month progression with an odds ratio (OR) of 6.69 (P &lt; .01) for PanNETs and 5.88 (P &lt; .003) for midgut NETs. The same thresholds were found to be optimal for predicting death at 36 months, with an OR of 2.87 (P &lt; .03) and 5.09 (P &lt; .005) for PanNETs and midgut NETs, respectively. In multivariate Cox hazard regression analysis for PFS in PanNETs, 1 or greater CTC had a hazard ratio (HR) of 2.6 (P &lt; .01), whereas 2 or greater CTCs had an HR of 2.25 (P &lt; .01) in midgut NETs. In multivariate analysis OS in PanNETs, 1 or greater CTCs had an HR of 3.16 (P &lt; .01) and in midgut NETs, 2 or greater CTCs had an HR of 1.73 (P &lt; .06). Conclusions The optimal CTC threshold to predict PFS and OS in metastatic PanNETs and midgut NETs is 1 and 2, respectively. These thresholds can be used to stratify patients in clinical practice and clinical trials.

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