Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Circulating Tumor Cells: The Next Generation Liquid Biopsy

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 22542

Share This Special Issue

Special Issue Editor

Dr. Andi Cani

E-Mail Website
Guest Editor

Hematology/Oncology Division, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
Interests: cancer liquid biopsy; circulating tumor cells; circulating tumor DNA; precision oncology; immuno-oncology; tumor evolution

Special Issue Information

Dear Colleagues,

Circulating tumor cells (CTC) are cancer cells that leave a primary or metastatic lesion and are found in blood circulation. As such, they are thought to enable cancer dissemination and metastatic spread. This was confirmed by the discovery two decades ago that high CTC counts portend a poor prognosis in several major cancer types. Since then, technological advances have allowed CTC researchers to move beyond their enumeration and make strides toward the characterization of the CTC phenotype in terms of protein expression as well as their genomic and transcriptomic makeup. More recently, single cell technologies have entered the CTC field, promising to enhance our cellular and molecular understanding of cancer with the ultimate goal of improving patient outcomes.

This all-encompassing Special Issue, “Circulating Tumor Cells: Next Generation Liquid Biopsy”, aims to present the latest CTC research including but not limited to:

CTC genomics and transcriptomics for liquid biopsy-driven detection of actionable alterations;
CTC and circulating tumor DNA (ctDNA) as cancer liquid biopsy approaches providing complementary information;
The CTC epigenome;
Protein/proteome studies in CTC;
CTC and the invasion-metastasis cascade;
Technological advances in CTC capture, purification, and analysis;
CTC in cerebrospinal fluid (CSF);
CTC viability and maintenance using in vitro cultures and in vivo xenografts.

Dr. Andi Cani
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

circulating tumor cells, CTCs
liquid biopsy
precision oncology
next-generation sequencing, NGS
circulating tumor DNA, ctDNA
cancer genomics
cancer transcriptomics
cancer epigenetics
cancer proteomics
CTC prognosis
CTC technology

Published Papers (6 papers)

Download All Papers

Research

Jump to: Review

15 pages, 2131 KiB

Open AccessArticle

Characterization of BCMA Expression in Circulating Rare Single Cells of Patients with Plasma Cell Neoplasms

by Libere J. Ndacayisaba, Kate E. Rappard, Stephanie N. Shishido, Sonia M. Setayesh, Guilin Tang, Pei Lin, Nicholas Matsumoto, Ching-Ju Hsu, Rafael Nevarez, Carmen Ruiz Velasco, Amin Naghdloo, Eric Yang, Kevin Kelly, James Hicks, Jeremy Mason, Robert Z. Orlowski, Elisabet E. Manasanch and Peter Kuhn

Int. J. Mol. Sci. 2022, 23(21), 13427; https://doi.org/10.3390/ijms232113427 - 03 Nov 2022

Viewed by 3320

Abstract

B-cell maturation antigen (BCMA), a key regulator of B-cell proliferation and survival, is highly expressed in almost all cases of plasma cell neoplasms and B-lymphoproliferative malignancies. BCMA is a robust biomarker of plasma cells and a therapeutic target with substantial clinical significance. However, the expression of BCMA in circulating tumor cells of patients with hematological malignancies has not been validated for the detection of circulating plasma and B cells. The application of BCMA as a biomarker in single-cell detection and profiling of circulating tumor cells in patients’ blood could enable early disease profiling and therapy response monitoring. Here, we report the development and validation of a slide-based immunofluorescence assay (i.e., CD138, BCMA, CD45, DAPI) for enrichment-free detection, quantification, and morphogenomic characterization of BCMA-expressing cells in patients (N = 9) with plasma cell neoplasms. Varying morphological subtypes of circulating BCMA-expressing cells were detected across the CD138(+/−) and CD45(+/−) compartments, representing candidate clonotypic post-germinal center B cells, plasmablasts, and both normal and malignant plasma cells. Genomic analysis by single-cell sequencing and correlation to clinical FISH cytogenetics provides validation, with data showing that patients across the different neoplastic states carry both normal and altered BCMA-expressing cells. Furthermore, altered cells harbor cytogenetic events detected by clinical FISH. The reported enrichment-free liquid biopsy approach has potential applications as a single-cell methodology for the early detection of BCMA+ B-lymphoid malignancies and in monitoring therapy response for patients undergoing anti-BCMA treatments. Full article

(This article belongs to the Special Issue Circulating Tumor Cells: The Next Generation Liquid Biopsy)

► Show Figures

Figure 1

16 pages, 2248 KiB

Open AccessArticle

Integrated Workflow for the Label-Free Isolation and Genomic Analysis of Single Circulating Tumor Cells in Pancreatic Cancer

by Brittany Rupp, Sarah Owen, Harrison Ball, Kaylee Judith Smith, Valerie Gunchick, Evan T. Keller, Vaibhav Sahai and Sunitha Nagrath

Int. J. Mol. Sci. 2022, 23(14), 7852; https://doi.org/10.3390/ijms23147852 - 16 Jul 2022

Cited by 2 | Viewed by 2351

Abstract

As pancreatic cancer is the third deadliest cancer in the U.S., the ability to study genetic alterations is necessary to provide further insight into potentially targetable regions for cancer treatment. Circulating tumor cells (CTCs) represent an especially aggressive subset of cancer cells, capable of causing metastasis and progressing the disease. Here, we present the Labyrinth–DEPArray pipeline for the isolation and analysis of single CTCs. Established cell lines, patient-derived CTC cell lines and freshly isolated CTCs were recovered and sequenced to reveal single-cell copy number variations (CNVs). The resulting CNV profiles of established cell lines showed concordance with previously reported data and highlight several gains and losses of cancer-related genes such as FGFR3 and GNAS. The novel sequencing of patient-derived CTC cell lines showed gains in chromosome 8q, 10q and 17q across both CTC cell lines. The pipeline was used to process and isolate single cells from a metastatic pancreatic cancer patient revealing a gain of chromosome 1q and a loss of chromosome 5q. Overall, the Labyrinth-DEPArray pipeline offers a validated workflow combining the benefits of antigen-free CTC isolation with single cell genomic analysis. Full article

(This article belongs to the Special Issue Circulating Tumor Cells: The Next Generation Liquid Biopsy)

► Show Figures

Figure 1

14 pages, 2038 KiB

Open AccessArticle

Multigene Profiling of Circulating Tumor Cells (CTCs) for Prognostic Assessment in Treatment-Naïve Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

by Zachery R. Reichert, Tadas Kasputis, Srinivas Nallandhighal, Sophia M. Abusamra, Amy Kasputis, Saloni Haruray, Yugang Wang, Shamara Williams, Udit Singhal, Ajjai Alva, Frank C. Cackowski, Megan E. V. Caram, Phillip L. Palmbos, Sarah E. Yentz, David C. Smith, Joshi J. Alumkal and Todd M. Morgan

Int. J. Mol. Sci. 2022, 23(1), 4; https://doi.org/10.3390/ijms23010004 - 21 Dec 2021

Cited by 6 | Viewed by 2786

Abstract

The substantial biological heterogeneity of metastatic prostate cancer has hindered the development of personalized therapeutic approaches. Therefore, it is difficult to predict the course of metastatic hormone-sensitive prostate cancer (mHSPC), with some men remaining on first-line androgen deprivation therapy (ADT) for several years while others progress more rapidly. Improving our ability to risk-stratify patients would allow for the optimization of systemic therapies and support the development of stratified prospective clinical trials focused on patients likely to have the greatest potential benefit. Here, we applied a liquid biopsy approach to identify clinically relevant, blood-based prognostic biomarkers in patients with mHSPC. Gene expression indicating the presence of CTCs was greater in CHAARTED high-volume (HV) patients (52% CTC_high) than in low-volume (LV) patients (23% CTC_high; * p = 0.03). HV disease (p = 0.005, q = 0.033) and CTC presence at baseline prior to treatment initiation (p = 0.008, q = 0.033) were found to be independently associated with the risk of nonresponse at 7 months. The pooled gene expression from CTCs of pre-ADT samples found AR, DSG2, KLK3, MDK, and PCA3 as genes predictive of nonresponse. These observations support the utility of liquid biomarker approaches to identify patients with poor initial response. This approach could facilitate more precise treatment intensification in the highest risk patients. Full article

(This article belongs to the Special Issue Circulating Tumor Cells: The Next Generation Liquid Biopsy)

► Show Figures

Figure 1

Review

Jump to: Research

39 pages, 7060 KiB

Open AccessReview

Microfluidic-Based Technologies for CTC Isolation: A Review of 10 Years of Intense Efforts towards Liquid Biopsy

by Lucie Descamps, Damien Le Roy and Anne-Laure Deman

Int. J. Mol. Sci. 2022, 23(4), 1981; https://doi.org/10.3390/ijms23041981 - 10 Feb 2022

Cited by 49 | Viewed by 4652

Abstract

The selection of circulating tumor cells (CTCs) directly from blood as a real-time liquid biopsy has received increasing attention over the past ten years, and further analysis of these cells may greatly aid in both research and clinical applications. CTC analysis could advance understandings of metastatic cascade, tumor evolution, and patient heterogeneity, as well as drug resistance. Until now, the rarity and heterogeneity of CTCs have been technical challenges to their wider use in clinical studies, but microfluidic-based isolation technologies have emerged as promising tools to address these limitations. This review provides a detailed overview of latest and leading microfluidic devices implemented for CTC isolation. In particular, this study details must-have device performances and highlights the tradeoff between recovery and purity. Finally, the review gives a report of CTC potential clinical applications that can be conducted after CTC isolation. Widespread microfluidic devices, which aim to support liquid-biopsy-based applications, will represent a paradigm shift for cancer clinical care in the near future. Full article

(This article belongs to the Special Issue Circulating Tumor Cells: The Next Generation Liquid Biopsy)

► Show Figures

Figure 1

19 pages, 1317 KiB

Open AccessReview

Circulating Tumor Cells in Hepatocellular Carcinoma: A Comprehensive Review and Critical Appraisal

by María Lola Espejo-Cruz, Sandra González-Rubio, Javier Zamora-Olaya, Víctor Amado-Torres, Rafael Alejandre, Marina Sánchez-Frías, Rubén Ciria, Manuel De la Mata, Manuel Rodríguez-Perálvarez and Gustavo Ferrín

Int. J. Mol. Sci. 2021, 22(23), 13073; https://doi.org/10.3390/ijms222313073 - 03 Dec 2021

Cited by 11 | Viewed by 4015

Abstract

Hepatocellular carcinoma (HCC) is the fifth most common neoplasm and a major cause of cancer-related death worldwide. There is no ideal biomarker allowing early diagnosis of HCC and tumor surveillance in patients receiving therapy. Liquid biopsy, and particularly circulating tumor cells (CTCs), have emerged as a useful tool for diagnosis and monitoring therapeutic responses in different tumors. In the present manuscript, we evaluate the current evidence supporting the quantitative and qualitative assessment of CTCs as potential biomarkers of HCC, as well as technical aspects related to isolation, identification, and classification of CTCs. Although the dynamic assessment of CTCs in patients with HCC may aid the decision-making process, there are still many uncertainties and technical caveats to be solved before this methodology has a true impact on clinical practice guidelines. More studies are needed to identify the optimal combination of surface markers, to increase the efficiency of ex-vivo expansion of CTCs, or even to target CTCs as a potential therapeutic strategy to prevent HCC recurrence after surgery or to hamper tumor progression and extrahepatic spreading. Full article

(This article belongs to the Special Issue Circulating Tumor Cells: The Next Generation Liquid Biopsy)

► Show Figures

Figure 1

26 pages, 1655 KiB

Open AccessReview

Liquid Biopsy in Melanoma: Significance in Diagnostics, Prediction and Treatment Monitoring

by Paula Kamińska, Karolina Buszka, Maciej Zabel, Michał Nowicki, Catherine Alix-Panabières and Joanna Budna-Tukan

Int. J. Mol. Sci. 2021, 22(18), 9714; https://doi.org/10.3390/ijms22189714 - 08 Sep 2021

Cited by 19 | Viewed by 4207

Abstract

Liquid biopsy is a common term referring to circulating tumor cells and other biomarkers, such as circulating tumor DNA (ctDNA) or extracellular vesicles. Liquid biopsy presents a range of clinical advantages, such as the low invasiveness of the blood sample collection and continuous control of the tumor progression. In addition, this approach enables the mechanisms of drug resistance to be determined in various methods of cancer treatment, including immunotherapy. However, in the case of melanoma, the application of liquid biopsy in patient stratification and therapy needs further investigation. This review attempts to collect all of the relevant and recent information about circulating melanoma cells (CMCs) related to the context of malignant melanoma and immunotherapy. Furthermore, the biology of liquid biopsy analytes, including CMCs, ctDNA, mRNA and exosomes, as well as techniques for their detection and isolation, are also described. The available data support the notion that thoughtful selection of biomarkers and technologies for their detection can contribute to the development of precision medicine by increasing the efficacy of cancer diagnostics and treatment. Full article

(This article belongs to the Special Issue Circulating Tumor Cells: The Next Generation Liquid Biopsy)

► Show Figures