scholarly journals Circulating Tumor Cells (CTCs): A Unique Model of Cancer Metastases and Non-invasive Biomarkers of Therapeutic Response

2021 ◽  
Vol 12 ◽  
Author(s):  
Jialing Liu ◽  
Jingru Lian ◽  
Yafei Chen ◽  
Xin Zhao ◽  
ChangZheng Du ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Metastasis ◽  
Therapeutic Response ◽  
Ex Vivo ◽  
Short Review ◽  
Metastatic Progression ◽  
Culture Techniques ◽  
Non Invasive ◽  
Metastatic Sites

Late-stage cancer metastasis remains incurable in the clinic and is the major cause death in patients. Circulating tumor cells (CTCs) are thought to be metastatic precursors shed from the primary tumor or metastatic deposits and circulate in the blood. The molecular network regulating CTC survival, extravasation, and colonization in distant metastatic sites is poorly defined, largely due to challenges in isolating rare CTCs. Recent advances in CTC isolation and ex vivo culture techniques facilitates single-cell omics and the development of related animal models to study CTC-mediated metastatic progression. With these powerful tools, CTCs can potentially be used as non-invasive biomarkers predicting therapeutic response. These studies may open a new avenue for CTC-specific drug discoveries. In this short review, we aim to summarize recent progress in the characterization of CTCs and their clinical relevance in various cancers, setting the stage for realizing personalized therapies against metastases.

scholarly journals A Novel Ex Vivo System Using 3D Polymer Scaffold to Culture Circulating Tumor Cells from Breast Cancer Patients Exhibits Dynamic E-M Phenotypes

2019 ◽  
Vol 8 (9) ◽  
pp. 1473 ◽  
Author(s):  
Tamasa De ◽  
Shina Goyal ◽  
Gowri Balachander ◽  
Kaushik Chatterjee ◽  
Prashant Kumar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patient ◽  
Breast Cancer Patient ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Ex Vivo ◽  
Blood Samples ◽  
Mesenchymal Transition

The majority of the cancer-associated deaths is due to metastasis—the spread of tumors to other organs. Circulating tumor cells (CTCs), which are shed from the primary tumor into the circulation, serve as precursors of metastasis. CTCs have now gained much attention as a new prognostic and diagnostic marker, as well as a screening tool for patients with metastatic disease. However, very little is known about the biology of CTCs in cancer metastasis. An increased understanding of CTC biology, their heterogeneity, and interaction with other cells can help towards a better understanding of the metastatic process, as well as identify novel drug targets. Here we present a novel ex vivo 3D system for culturing CTCs from breast cancer patient blood samples using porous poly(ε-caprolactone) (PCL) scaffolds. As a proof of principle study, we show that ex vivo culture of 12/16 (75%) advanced stage breast cancer patient blood samples were enriched for CTCs identified as CK+ (cytokeratin positive) and CD45− (CD45 negative) cells. The deposition of extracellular matrix proteins on the PCL scaffolds permitted cellular attachment to these scaffolds. Detection of Ki-67 and bromodeoxyuridine (BrdU) positive cells revealed proliferating cell population in the 3D scaffolds. The CTCs cultured without prior enrichment exhibited dynamic differences in epithelial (E) and mesenchymal (M) composition. Thus, our 3D PCL scaffold system offers a physiologically relevant model to be used for studying CTC biology as well as for individualized testing of drug susceptibility. Further studies are warranted for longitudinal monitoring of epithelial–mesenchymal transition (EMT) in CTCs for clinical association.

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 Circulating Tumor Cells from Enumeration to Analysis: Current Challenges and Future Opportunities

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2723
Author(s):  
Yu-Ping Yang ◽  
Teresa M. Giret ◽  
Richard J. Cote
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Ex Vivo ◽  
Detection Sensitivity ◽  
Clinical Utilization ◽  
Diagnosis And Prognosis ◽  
Early Cancer Diagnosis ◽  
Potential Marker ◽  
Potential Applications ◽  
Downstream Analysis

Circulating tumor cells (CTCs) have been recognized as a major contributor to distant metastasis. Their unique role as metastatic seeds renders them a potential marker in the circulation for early cancer diagnosis and prognosis as well as monitoring of therapeutic response. In the past decade, researchers mainly focused on the development of isolation techniques for improving the recovery rate and purity of CTCs. These developed techniques have significantly increased the detection sensitivity and enumeration accuracy of CTCs. Currently, significant efforts have been made toward comprehensive molecular characterization, ex vivo expansion of CTCs, and understanding the interactions between CTCs and their associated cells (e.g., immune cells and stromal cells) in the circulation. In this review, we briefly summarize existing CTC isolation technologies and specifically focus on advances in downstream analysis of CTCs and their potential applications in precision medicine. We also discuss the current challenges and future opportunities in their clinical utilization.

The Clinical Application of Circulating Tumor Cells and DNAs as Prognostic and Predictive Biomarkers in Gastrointestinal Cancer

2021 ◽  
Vol 21 ◽  
Author(s):  
Sara Memarpour ◽  
Ghazaleh Khalili-Tanha ◽  
Awa Alizadeh Ghannad ◽  
Masoud Sharifian Razavi ◽  
Mona Joudi ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Tumor Biology ◽  
Predictive Biomarkers ◽  
Invasive Approach ◽  
New Approach ◽  
Non Invasive ◽  
Gi Cancer ◽  
Gi Cancers ◽  
Tumor Dna

: Gastrointestinal (GI) cancer is one of the most common cancers globally. Genetic and epigenetic mechanisms are involved in its pathogenesis. The conventional methods for diagnosis and screening for GI cancers are often invasive and have other limitations. In the era of personalized medicine, a novel non-invasive approach called liquid biopsy has been introduced for the detection and management of GI cancers, which focuses on the analysis of circulating tumor cells (CTCs) and circulating cell-free tumor DNA (ctDNA). Several studies have shown that this new approach allows for an improved understanding of GI tumor biology and will lead to an improvement in clinical management. The aim of the current review is to explore the clinical applications of CTCs and ctDNA in patients with GI cancer.

scholarly journals A small molecule screen identified N-Acetyl-L-cysteine for promoting ex vivo growth of single circulating tumor cells

2020 ◽  
Author(s):  
Teng Teng ◽  
Mohamed Kamal ◽  
Oihana Iriondo ◽  
Yonatan Amzaleg ◽  
Chunqiao Luo ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Small Molecule ◽  
Ex Vivo ◽  
Single Cells ◽  
Small Subset ◽  
Blood Draw ◽  
Small Molecule Screen ◽  
Functional Analyses ◽  
Single Ctcs

AbstractCirculating tumor cells (CTCs) can be isolated via a minimally invasive blood draw and are considered a “liquid biopsy” of their originating solid tumors. CTCs contain a small subset of metastatic precursors that can form metastases in secondary organs, and provide a resource to identify mechanisms underlying metastasis-initiating properties. Despite technological advancements that allow for highly sensitive approaches of detection and isolation, CTCs are very rare and often present as single cells, posing an extreme challenge for ex vivo expansion after isolation. Here, using previously established patient-derived CTC lines, we performed a small molecule drug screening to identify compounds that can improve ex vivo culture efficiency for single CTCs. We found that N-acetylcysteine (NAC) and other antioxidants can promote ex vivo expansion of single CTCs, by reducing oxidative and other stress particularly at the initial stage of single cell expansion. RNA-seq analysis of growing clones and non-growing clones confirmed the effect by NAC, but also indicate that NAC-induced decrease in oxidative stress is insufficient for promoting proliferation of a subset of cells with heterogeneous quiescent and senescent features. Despite the challenge in expanding all CTCs, NAC treatment lead to establishment of single CTC clones that have similar tumorigenic features, which will facilitate future functional analyses.

scholarly journals A Digital RNA Signature of Circulating Tumor Cells Predicting Early Therapeutic Response in Localized and Metastatic Breast Cancer

2018 ◽  
Vol 8 (10) ◽  
pp. 1286-1299 ◽  
Author(s):  
Tanya T. Kwan ◽  
Aditya Bardia ◽  
Laura M. Spring ◽  
Anita Giobbie-Hurder ◽  
Mark Kalinich ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Therapeutic Response ◽  
Metastatic Breast ◽  
Rna Signature

Circulating Tumor Cells (CTCs) for Comprehensive and Multiregional Non-Invasive Genetic Characterization of Multiple Myeloma (MM)

2019 ◽  
Vol 19 (10) ◽  
pp. e351
Author(s):  
Juan José Garcés ◽  
Gabriel Bretones ◽  
Leire Burgos ◽  
Rafael Valdés-Mas ◽  
Diego Alignani ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Genetic Characterization ◽  
Non Invasive

scholarly journals Nanoemulsions to support ex vivo cell culture of breast cancer circulating tumor cells

2020 ◽  
Vol 16 ◽  
pp. 100265
Author(s):  
N. Carmona-Ule ◽  
C. Abuín-Redondo ◽  
C. Costa ◽  
R. Piñeiro ◽  
T. Pereira-Veiga ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Culture ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Ex Vivo

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 Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value

2020 ◽  
Vol 21 (5) ◽  
pp. 1671 ◽  
Author(s):  
Anna Fabisiewicz ◽  
Malgorzata Szostakowska-Rodzos ◽  
Anna J. Zaczek ◽  
Ewa A. Grzybowska
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Cancer Biology ◽  
Cancer Metastasis ◽  
Metastatic Breast ◽  
Breast Cancer Metastasis ◽  
Current Status ◽  
Molecular Profile ◽  
Breast Cancer Patients

Breast cancer metastasis is the leading cause of cancer deaths in women and is difficult to combat due to the long periods in which disseminated cells retain a potential to be re-activated and start the relapse. Assessing the number and molecular profile of circulating tumor cells (CTCs) in breast cancer patients, especially in early breast cancer, should help in identifying the possibility of relapse in time for therapeutic intervention to prevent or delay recurrence. While metastatic breast cancer is considered incurable, molecular analysis of CTCs still have a potential to define particular susceptibilities of the cells representing the current tumor burden, which may differ considerably from the cells of the primary tumor, and offer more tailored therapy to the patients. In this review we inspect the routes to metastasis and how they can be linked to specific features of CTCs, how CTC analysis may be used in therapy, and what is the current status of the research and efforts to include CTC analysis in clinical practice.

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