Special Issue "Circulating Tumor Cells as Cancer Diagnostic Biomarkers"

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Molecular Diagnosis".

Deadline for manuscript submissions: closed (3 August 2018)

Special Issue Editor

Guest Editor
Prof. Dr. Dario Marchetti

Director, Biomarker Research Program, Houston Methodist Research Institute, Professor, Institute of Academic Medicine, Visiting Professor, Baylor College of Medicine, MS: R7-414, 6670 Bertner Avenue, Houston, TX 77030, USA
Website | E-Mail
Interests: the biology and therapeutic utility of circulating tumor cells (CTCs); liquid biopsies; mechanisms of brain metastasis and dormancy in breast and melanoma cancers; roles of heparanase in development and disease

Special Issue Information

Dear Colleagues,

The major cause of cancer mortality is metastasis; however, the mechanisms of clinical metastasis remain poorly understood. Because tumor cell dissemination mostly occurs through the blood, deciphering biomarkers, properties and characteristics of circulating tumor cells (CTCs) are of fundamental relevance to develop and implement novel drug therapies in oncology. CTCs can act as “liquid biopsy” to diagnose and monitor cancer in patients in “real time”. They represent clinically useful tools to better reflect cancer progression, nascent metastatic disease, and therapy efficacy in the patient.

There are multiple challenges connected with CTC research and CTC clinical implementation. CTCs are rare, fragile, and heterogeneous, latter either inherited from respective primary/metastatic tumors or as a result of CTC properties interconversion by genetic/epigenetic progression that may or may not lead to a fully metastatic-competent CTC.  Significant technical challenges in the field also persist to identify and interrogate CTC heterogeneity, discover CTC biomarkers of clinical utility, and comprehensively capture and interrogate CTCs. Many studies have reported the clinical impact of CTCs since CTC testing has being applied in over 300 clinical trials worldwide. However, much of the CTC biology needs to be discovered and many scientific/technical challenges must be overcome before their clinical promise as biomarkers and targets for improved therapies can be fulfilled.

The objective of this Special Issue is to publish latest findings of CTC research. Contributions outlining CTC discoveries in biological and clinical settings, CTC theoretical and pre-clinical models, CTC technologies and methods for their detection, and clinical findings applying CTC concepts, are welcome.

Prof. Dr. Dario Marchetti
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Diagnostics is an international peer-reviewed open access quarterly journal published by MDPI.

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Keywords

  • CTCs
  • Liquid Biopsy
  • Cancer metastasis
  • The biology and therapeutic utility of CTCs
  • CTC technologies
  • Tumor dormancy
  • Mechanisms of metastasis

Published Papers (6 papers)

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Review

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Open AccessReview Circulating Tumor Cells for the Management of Renal Cell Carcinoma
Diagnostics 2018, 8(3), 63; https://doi.org/10.3390/diagnostics8030063
Received: 7 August 2018 / Revised: 30 August 2018 / Accepted: 31 August 2018 / Published: 3 September 2018
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Abstract
Renal cell carcinoma is a highly malignant cancer that would benefit from non-invasive innovative markers providing early diagnosis and recurrence detection. Circulating tumor cells are a particularly promising marker of tumor invasion that could be used to improve the management of patients with
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Renal cell carcinoma is a highly malignant cancer that would benefit from non-invasive innovative markers providing early diagnosis and recurrence detection. Circulating tumor cells are a particularly promising marker of tumor invasion that could be used to improve the management of patients with RCC. However, the extensive genetic and immunophenotypic heterogeneity of cells from RCC and their trend to transition to the mesenchymal phenotype when they circulate in blood constitute a challenge for their sensitive and specific detection. This review analyzes published studies targeting CTC in patients with RCC, in the context of the biological, pathological, and molecular complexity of this particular cancer. Although further analytical and clinical studies are needed to pinpoint the most suitable approach for highly sensitive CTC detection in RCC patients, it is clear that this field can bring a relevant guide to clinicians and help to RCC patients. Furthermore, as described, a particular subtype of RCC—the ccRCC—can be used as a model to study the relationship between cytomorphological and genetic cellular markers of malignancy, an important issue for the study of CTC from any type of solid cancer. Full article
(This article belongs to the Special Issue Circulating Tumor Cells as Cancer Diagnostic Biomarkers)
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Open AccessReview The Interplay between Circulating Tumor Cells and the Immune System: From Immune Escape to Cancer Immunotherapy
Diagnostics 2018, 8(3), 59; https://doi.org/10.3390/diagnostics8030059
Received: 24 July 2018 / Revised: 20 August 2018 / Accepted: 28 August 2018 / Published: 30 August 2018
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Abstract
Circulating tumor cells (CTCs) have aroused increasing interest not only in mechanistic studies of metastasis, but also for translational applications, such as patient monitoring, treatment choice, and treatment change due to tumor resistance. In this review, we will assess the state of the
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Circulating tumor cells (CTCs) have aroused increasing interest not only in mechanistic studies of metastasis, but also for translational applications, such as patient monitoring, treatment choice, and treatment change due to tumor resistance. In this review, we will assess the state of the art about the study of the interactions between CTCs and the immune system. We intend to analyze the impact that the cells of the immune system have in limiting or promoting the metastatic capability of CTCs. To this purpose, we will examine studies that correlate CTCs, immune cells, and patient prognosis, and we will also discuss relevant animal models that have contributed to the understanding of the mechanisms of immune-mediated metastasis. We will then consider some studies in which CTCs seem to play a promising role in monitoring cancer patients during immunotherapy regimens. We believe that, from an accurate and profound knowledge of the interactions between CTCs and the immune system, new immunotherapeutic strategies against cancer might emerge in the future. Full article
(This article belongs to the Special Issue Circulating Tumor Cells as Cancer Diagnostic Biomarkers)
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Open AccessReview Cancer Diagnosis Using a Liquid Biopsy: Challenges and Expectations
Diagnostics 2018, 8(2), 31; https://doi.org/10.3390/diagnostics8020031
Received: 15 April 2018 / Revised: 4 May 2018 / Accepted: 7 May 2018 / Published: 9 May 2018
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Abstract
The field of cancer diagnostics has recently been impacted by new and exciting developments in the area of liquid biopsy. A liquid biopsy is a minimally invasive alternative to surgical biopsies of solid tissues, typically achieved through the withdrawal of a blood sample
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The field of cancer diagnostics has recently been impacted by new and exciting developments in the area of liquid biopsy. A liquid biopsy is a minimally invasive alternative to surgical biopsies of solid tissues, typically achieved through the withdrawal of a blood sample or other body fluids, allowing the interrogation of tumor-derived material including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) fragments that are present at a given time point. In this short review, we discuss a few studies that summarize the state-of-the-art in the liquid biopsy field from a diagnostic perspective, and speculate on current challenges and expectations of implementing liquid biopsy testing for cancer diagnosis and monitoring in the clinical setting. Full article
(This article belongs to the Special Issue Circulating Tumor Cells as Cancer Diagnostic Biomarkers)
Open AccessReview Circulating Tumor Cell Analysis in Preclinical Mouse Models of Metastasis
Diagnostics 2018, 8(2), 30; https://doi.org/10.3390/diagnostics8020030
Received: 1 April 2018 / Revised: 24 April 2018 / Accepted: 24 April 2018 / Published: 28 April 2018
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Abstract
The majority of cancer deaths occur because of metastasis since current therapies are largely non-curative in the metastatic setting. The use of in vivo preclinical mouse models for assessing metastasis is, therefore, critical for developing effective new cancer biomarkers and therapies. Although a
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The majority of cancer deaths occur because of metastasis since current therapies are largely non-curative in the metastatic setting. The use of in vivo preclinical mouse models for assessing metastasis is, therefore, critical for developing effective new cancer biomarkers and therapies. Although a number of quantitative tools have been previously developed to study in vivo metastasis, the detection and quantification of rare metastatic events has remained challenging. This review will discuss the use of circulating tumor cell (CTC) analysis as an effective means of tracking and characterizing metastatic disease progression in preclinical mouse models of breast and prostate cancer and the resulting lessons learned about CTC and metastasis biology. We will also discuss how the use of clinically-relevant CTC technologies such as the CellSearch® and Parsortix™ platforms for preclinical CTC studies can serve to enhance the study of cancer biology, new biomarkers, and novel therapies from the bench to the bedside. Full article
(This article belongs to the Special Issue Circulating Tumor Cells as Cancer Diagnostic Biomarkers)
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Open AccessReview Aneuploid CTC and CEC
Diagnostics 2018, 8(2), 26; https://doi.org/10.3390/diagnostics8020026
Received: 11 March 2018 / Revised: 16 April 2018 / Accepted: 17 April 2018 / Published: 18 April 2018
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Abstract
Conventional circulating tumor cell (CTC) detection technologies are restricted to large tumor cells (> white blood cells (WBCs)), or those unique carcinoma cells with double positive expression of surface epithelial cell adhesion molecule (EpCAM) for isolation, and intracellular structural protein cytokeratins (CKs) for
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Conventional circulating tumor cell (CTC) detection technologies are restricted to large tumor cells (> white blood cells (WBCs)), or those unique carcinoma cells with double positive expression of surface epithelial cell adhesion molecule (EpCAM) for isolation, and intracellular structural protein cytokeratins (CKs) for identification. With respect to detecting the full spectrum of highly heterogeneous circulating rare cells (CRCs), including CTCs and circulating endothelial cells (CECs), it is imperative to develop a strategy systematically coordinating all tri-elements of nucleic acids, biomarker proteins, and cellular morphology, to effectively enrich and comprehensively identify CRCs. Accordingly, a novel strategy integrating subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH), independent of cell size variation and free of hypotonic damage as well as anti-EpCAM perturbing, has been demonstrated to enable in situ phenotyping multi-protein expression, karyotyping chromosome aneuploidy, and detecting cytogenetic rearrangements of the ALK gene in non-hematologic CRCs. Symbolic non-synonymous single nucleotide variants (SNVs) of both the TP53 gene (P33R) in each single aneuploid CTCs, and the cyclin-dependent kinase inhibitor 2A (CDKN2A) tumor suppressor gene in each examined aneuploid CECs, were identified for the first time across patients with diverse carcinomas. Comprehensive co-detecting observable aneuploid CTCs and CECs by SE-iFISH, along with applicable genomic and/or proteomic single cell molecular profiling, are anticipated to facilitate elucidating how those disparate categories of aneuploid CTCs and CECs cross-talk and functionally interplay with tumor angiogenesis, therapeutic drug resistance, tumor progression, and cancer metastasis. Full article
(This article belongs to the Special Issue Circulating Tumor Cells as Cancer Diagnostic Biomarkers)
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Other

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Open AccessOpinion Perspective on Cancer Therapeutics Utilizing Analysis of Circulating Tumor Cells
Diagnostics 2018, 8(2), 23; https://doi.org/10.3390/diagnostics8020023
Received: 19 March 2018 / Revised: 3 April 2018 / Accepted: 9 April 2018 / Published: 11 April 2018
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Abstract
Various methods are available for cancer screening, and the methods are performed depending on the origin site of cancer. Among these methods, biopsy followed by medical imaging is the most common. After cancer progression is determined, an optimal treatment—such as surgery, chemotherapy, and/or
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Various methods are available for cancer screening, and the methods are performed depending on the origin site of cancer. Among these methods, biopsy followed by medical imaging is the most common. After cancer progression is determined, an optimal treatment—such as surgery, chemotherapy, and/or radiation therapy—is selected. A new assay has been developed that detects circulating tumor cells (CTCs). Tracking changes in CTCs may reveal important tumoral sensitivity information or resistance patterns to specific regimens and prompt changes in therapy on a personalized basis. Characterization of CTCs at the DNA, RNA, and protein levels is important for gaining insight for clinical applications. A small number of CTCs can be analyzed to obtain genome information such as the progression of cancer including metastasis, even in a single cluster. Although many clinical studies, particularly CTC enumeration and detection of specific oncogene expression, have increased the success rate of diagnosis and predicting prognosis, there is no consensus regarding the technical approaches and various aspects of the methodology, making it difficult to standardize optimal methods for CTC analysis. However, ongoing technological advances are currently being achieved and large-scale clinical studies are being conducted. Applying CTC analysis in the clinic would be very useful for advancing diagnosis, prognosis prediction, and therapeutics. Full article
(This article belongs to the Special Issue Circulating Tumor Cells as Cancer Diagnostic Biomarkers)
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