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Circulating Tumor Cells: From Research to Therapeutic Application
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Circulating Tumor Cells: From Research to Therapeutic Application

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 18073

Special Issue Editor

Prof. Dr. Dario Marchetti

E-Mail Website
Guest Editor
1. Division of Molecular Medicine, Department of Internal Medicine, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
2. Department of Pathology, The University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
3. Full Member, UNM Comprehensive Cancer Center, Albuquerque, NM 87131, USA
Interests: the biology and therapeutic utility of circulating tumor cells (CTCs); liquid biopsies; mechanisms of brain metastasis and dormancy in breast and melanoma cancers; molecular crosstalks between dormant bone-marrow (BM) cells and CTCs; roles of BM and BM cellular heterogeneity interplaying with metastasis and dormancy
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Special Issue Information

Dear Colleagues,

Circulating Tumor Cells (CTCs) comprise a rare and heterogeneous cell population that sheds from tumors and traverses the peripheral blood stream throughout the carcinogenic process, from early pre-malignant lesions to fatal metastasis. The concept of “Liquid Biopsy”-interrogating CTCs and other blood analytes (ctDNA, exosomes, microRNAs, etc.) for clinical application as precision medicine tools has significantly expanded in the last two decades, following the first implementation of liquid biopsy and proving the clinical utility of CTCs as independent prognostic indicators of progression-free and overall survival of metastatic cancer patients. Since then, the field of “Liquid Biopsy” has witnessed not only the development and commercialization of multiple platforms and tests, but also increased knowledge characterizing CTC biology, CTC subsets and CTC biomarkers. These advances have resulted in CTC analyses employing enrichment platforms that either capture CTCs by multiple parameters, at single-cell level, or that identify CTCs based on the expression of cancer-specific biomarkers or the presence of CTC-specific transcripts. Collectively, CTC studies have opened new investigational avenues towards the detection and prognostication of cancer progression and responses to therapy.

The objective of this Special Issue on CTCs is to publish the latest advances interrogating the biology and clinical implementation of CTCs. Contributions from diverse fields of expertise that outline the latest discoveries in CTC basic and translational research, including biological, genetic, technical, mathematical, pre-clinical and clinical advances, are welcome.

Prof. Dr. Dario Marchetti
Guest Editor

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Published Papers (3 papers)

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Research

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21 pages, 5531 KiB  
Article
Non-Invasive Profiling of Advanced Prostate Cancer via Multi-Parametric Liquid Biopsy and Radiomic Analysis
by Gareth Morrison, Jonathan Buckley, Dejerianne Ostrow, Bino Varghese, Steven Y. Cen, Jeffrey Werbin, Nolan Ericson, Alexander Cunha, Yi-Tsung Lu, Thaddeus George, Jeffrey Smith, David Quinn, Vinay Duddalwar, Timothy Triche and Amir Goldkorn
Int. J. Mol. Sci. 2022, 23(5), 2571; https://doi.org/10.3390/ijms23052571 - 25 Feb 2022
Cited by 9 | Viewed by 4810
Abstract
Integrating liquid biopsies of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) with other minimally invasive measures may yield more comprehensive disease profiles. We evaluated the feasibility of concurrent cellular and molecular analysis of CTCs and cfDNA combined with radiomic analysis of CT [...] Read more.
Integrating liquid biopsies of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) with other minimally invasive measures may yield more comprehensive disease profiles. We evaluated the feasibility of concurrent cellular and molecular analysis of CTCs and cfDNA combined with radiomic analysis of CT scans from patients with metastatic castration-resistant PC (mCRPC). CTCs from 22 patients were enumerated, stained for PC-relevant markers, and clustered based on morphometric and immunofluorescent features using machine learning. DNA from single CTCs, matched cfDNA, and buffy coats was sequenced using a targeted amplicon cancer hotspot panel. Radiomic analysis was performed on bone metastases identified on CT scans from the same patients. CTCs were detected in 77% of patients and clustered reproducibly. cfDNA sequencing had high sensitivity (98.8%) for germline variants compared to WBC. Shared and unique somatic variants in PC-related genes were detected in cfDNA in 45% of patients (MAF > 0.1%) and in CTCs in 92% of patients (MAF > 10%). Radiomic analysis identified a signature that strongly correlated with CTC count and plasma cfDNA level. Integration of cellular, molecular, and radiomic data in a multi-parametric approach is feasible, yielding complementary profiles that may enable more comprehensive non-invasive disease modeling and prediction. Full article
(This article belongs to the Special Issue Circulating Tumor Cells: From Research to Therapeutic Application)
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14 pages, 1464 KiB  
Article
CD74 and CD44 Expression on CTCs in Cancer Patients with Brain Metastasis
by Desiree Loreth, Moritz Schuette, Jenny Zinke, Malte Mohme, Andras Piffko, Svenja Schneegans, Julia Stadler, Melanie Janning, Sonja Loges, Simon A. Joosse, Katrin Lamszus, Manfred Westphal, Volkmar Müller, Markus Glatzel, Jakob Matschke, Christoffer Gebhardt, Stefan W. Schneider, Iwona Belczacka, Beate Volkmer, Rüdiger Greinert, Marie-Laure Yaspo, Patrick N. Harter, Klaus Pantel and Harriet Wikmanadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2021, 22(13), 6993; https://doi.org/10.3390/ijms22136993 - 29 Jun 2021
Cited by 34 | Viewed by 5198
Abstract
Up to 40% of advance lung, melanoma and breast cancer patients suffer from brain metastases (BM) with increasing incidence. Here, we assessed whether circulating tumor cells (CTCs) in peripheral blood can serve as a disease surrogate, focusing on CD44 and CD74 expression as [...] Read more.
Up to 40% of advance lung, melanoma and breast cancer patients suffer from brain metastases (BM) with increasing incidence. Here, we assessed whether circulating tumor cells (CTCs) in peripheral blood can serve as a disease surrogate, focusing on CD44 and CD74 expression as prognostic markers for BM. We show that a size-based microfluidic approach in combination with a semi-automated cell recognition system are well suited for CTC detection in BM patients and allow further characterization of tumor cells potentially derived from BM. CTCs were found in 50% (7/14) of breast cancer, 50% (9/18) of non-small cell lung cancer (NSCLC) and 36% (4/11) of melanoma patients. The next-generation sequencing (NGS) analysis of nine single CTCs from one breast cancer patient revealed three different CNV profile groups as well as a resistance causing ERS1 mutation. CD44 and CD74 were expressed on most CTCs and their expression was strongly correlated, whereas matched breast cancer BM tissues were much less frequently expressing CD44 and CD74 (negative in 46% and 54%, respectively). Thus, plasticity of CD44 and CD74 expression during trafficking of CTCs in the circulation might be the result of adaptation strategies. Full article
(This article belongs to the Special Issue Circulating Tumor Cells: From Research to Therapeutic Application)
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Review

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28 pages, 2517 KiB  
Review
Recent Advances in Methods for Circulating Tumor Cell Detection
by Monika Vidlarova, Alona Rehulkova, Pavel Stejskal, Andrea Prokopova, Hanus Slavik, Marian Hajduch and Josef Srovnal
Int. J. Mol. Sci. 2023, 24(4), 3902; https://doi.org/10.3390/ijms24043902 - 15 Feb 2023
Cited by 23 | Viewed by 7025
Abstract
Circulating tumor cells (CTCs) are released from primary tumors and transported through the body via blood or lymphatic vessels before settling to form micrometastases under suitable conditions. Accordingly, several studies have identified CTCs as a negative prognostic factor for survival in many types [...] Read more.
Circulating tumor cells (CTCs) are released from primary tumors and transported through the body via blood or lymphatic vessels before settling to form micrometastases under suitable conditions. Accordingly, several studies have identified CTCs as a negative prognostic factor for survival in many types of cancer. CTCs also reflect the current heterogeneity and genetic and biological state of tumors; so, their study can provide valuable insights into tumor progression, cell senescence, and cancer dormancy. Diverse methods with differing specificity, utility, costs, and sensitivity have been developed for isolating and characterizing CTCs. Additionally, novel techniques with the potential to overcome the limitations of existing ones are being developed. This primary literature review describes the current and emerging methods for enriching, detecting, isolating, and characterizing CTCs. Full article
(This article belongs to the Special Issue Circulating Tumor Cells: From Research to Therapeutic Application)
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