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Biomedicines
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The Biology of Circulating Tumor Cells 2.0
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The Biology of Circulating Tumor Cells 2.0

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: 15 December 2024 | Viewed by 9011

Special Issue Editor

Dr. Areti Strati

E-Mail Website
Guest Editor
Analysis of Circulating Tumor Cells Lab., Department of Chemistry, University of Athens, Athens, Greece
Interests: liquid biopsy; ddPCR; RT-qPCR; analytical validation; CTC; ctDNA
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The biology of circulating tumor cells (CTCs) has been of interest for over a century. However, despite the recent technical advancements, their isolation and detection remain a significant challenge, since their presence in the bloodstream represents a rare event. CTC analysis is a “liquid biopsy” approach that provides significant insights into tumor heterogeneity, the mechanisms of metastasis, tumor evolution and treatment resistance. Recent research discoveries have shown that the detection of tumor-specific biomarkers in CTCs could guide clinical decision-making. This Special Issue will focus on understanding the molecular mechanisms involved in CTCs’ presence in the bloodstream and cancer progression. More specifically, we will pay attention to current basic and preclinical research studies that provide significant insights into the biology of CTCs and the identification of specific biomarkers. Both original research and comprehensive reviews are welcome.

Dr. Areti Strati
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. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). 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

  • CTC
  • liquid biopsy
  • cancer biomarkers
  • prognostic value
  • predictive value
  • cancer
  • molecular characterization

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Related Special Issue

Published Papers (4 papers)

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Research

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11 pages, 1982 KiB  
Article
ES-SCLC Patients with PD-L1+ CTCs and High Percentages of CD8+PD-1+T Cells in Circulation Benefit from Front-Line Immunotherapy Treatment
by Anastasia Xagara, Argyro Roumeliotou, Alexandros Kokkalis, Konstantinos Tsapakidis, Dimitris Papakonstantinou, Vassilis Papadopoulos, Ioannis Samaras, Evagelia Chantzara, Galatea Kallergi and Athanasios Kotsakis
Biomedicines 2024, 12(1), 146; https://doi.org/10.3390/biomedicines12010146 - 10 Jan 2024
Cited by 1 | Viewed by 1729
Abstract
SCLC is an aggressive cancer type with high metastatic potential and bad prognosis. CTCs are a valuable source of tumor cells in blood circulation and are among the major contributors to metastasis. In this study we evaluated the number of CTCs that express [...] Read more.
SCLC is an aggressive cancer type with high metastatic potential and bad prognosis. CTCs are a valuable source of tumor cells in blood circulation and are among the major contributors to metastasis. In this study we evaluated the number of CTCs that express PD-L1 in treatment-naïve ES-SCLC patients receiving ICI in a front-line setting. Moreover, we explored the percentages of different immune T-cell subsets in circulation to assess their potential role in predicting responses. A total of 43 patients were enrolled—6 of them with LS-SCLC, and 37 with ES-SCLC disease. In addition, PBMCs from 10 healthy donors were used as a control group. Different T-cell subtypes were examined through multicolor FACS analysis and patients’ CTCs were detected using immunofluorescence staining. SCLC patients had higher percentages of PD-1-expressing CD3+CD4+ and CD3+CD8+ T-cells, as well as elevated PD-1 protein expression compared to healthy individuals. Additionally, in ES-SCLC patients, a positive correlation between CD3+CD8+PD-1+ T-cells and PD-L1+ CTCs was detected. Importantly, patients harboring higher numbers of CD3+CD8+PD-1+ T-cells together with PD-L1+CTCs had a survival advantage when receiving front-line immunotherapy. Thus, this study proposes, for first time possible, immune cell–CTCs interaction, as well as a potential novel clinical biomarker for ICI responses in ES-SCLC patients. Full article
(This article belongs to the Special Issue The Biology of Circulating Tumor Cells 2.0)
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16 pages, 2476 KiB  
Article
Hsp70—A Universal Biomarker for Predicting Therapeutic Failure in Human Female Cancers and a Target for CTC Isolation in Advanced Cancers
by Alexia Xanthopoulos, Ann-Kathrin Samt, Christiane Guder, Nicholas Taylor, Erika Roberts, Hannah Herf, Verena Messner, Anskar Trill, Katharina Larissa Kreszentia Holzmann, Marion Kiechle, Vanadin Seifert-Klauss, Sebastian Zschaeck, Imke Schatka, Robert Tauber, Robert Schmidt, Katrin Enste, Alan Graham Pockley, Dominik Lobinger and Gabriele Multhoff
Biomedicines 2023, 11(8), 2276; https://doi.org/10.3390/biomedicines11082276 - 16 Aug 2023
Cited by 5 | Viewed by 2301
Abstract
Heat shock protein 70 (Hsp70) is frequently overexpressed in many different tumor types. However, Hsp70 has also been shown to be selectively presented on the plasma membrane of tumor cells, but not normal cells, and this membrane form of Hsp70 (mHsp70) could be [...] Read more.
Heat shock protein 70 (Hsp70) is frequently overexpressed in many different tumor types. However, Hsp70 has also been shown to be selectively presented on the plasma membrane of tumor cells, but not normal cells, and this membrane form of Hsp70 (mHsp70) could be considered a universal tumor biomarker. Since viable, mHsp70-positive tumor cells actively release Hsp70 in lipid micro-vesicles, we investigated the utility of Hsp70 in circulation as a universal tumor biomarker and its potential as an early predictive marker of therapeutic failure. We have also evaluated mHsp70 as a target for the isolation and enumeration of circulating tumor cells (CTCs) in patients with different tumor entities. Circulating vesicular Hsp70 levels were measured in the peripheral blood of tumor patients with the compHsp70 ELISA. CTCs were isolated using cmHsp70.1 and EpCAM monoclonal antibody (mAb)-based bead approaches and characterized by immunohistochemistry using cytokeratin and CD45-specific antibodies. In two out of 35 patients exhibiting therapeutic failure two years after initial diagnosis of non-metastatic breast cancer, progressively increasing levels of circulating Hsp70 had already been observed during therapy, whereas levels in patients without subsequent recurrence remained unaltered. With regards to CTC isolation from patients with different tumors, an Hsp70 mAb-based selection system appears superior to an EpCAM mAb-based approach. Extracellular and mHsp70 can therefore serve as a predictive biomarker for therapeutic failure in early-stage tumors and as a target for the isolation of CTCs in various tumor diseases. Full article
(This article belongs to the Special Issue The Biology of Circulating Tumor Cells 2.0)
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Review

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23 pages, 1543 KiB  
Review
Circulating Tumor Cells: Origin, Role, Current Applications, and Future Perspectives for Personalized Medicine
by Maria Cristina Rapanotti, Tonia Cenci, Maria Giovanna Scioli, Elisa Cugini, Silvia Anzillotti, Luca Savino, Deborah Coletta, Cosimo Di Raimondo, Elena Campione, Mario Roselli, Sergio Bernardini, Luca Bianchi, Anastasia De Luca, Amedeo Ferlosio and Augusto Orlandi
Biomedicines 2024, 12(9), 2137; https://doi.org/10.3390/biomedicines12092137 - 20 Sep 2024
Cited by 1 | Viewed by 1715
Abstract
Circulating tumor cells (CTCs) currently represent a revolutionary tool offering unique insights for the evaluation of cancer progression, metastasis, and response to therapies. Indeed, CTCs, upon detachment from primary tumors, enter the bloodstream and acquire a great potential for their use for personalized [...] Read more.
Circulating tumor cells (CTCs) currently represent a revolutionary tool offering unique insights for the evaluation of cancer progression, metastasis, and response to therapies. Indeed, CTCs, upon detachment from primary tumors, enter the bloodstream and acquire a great potential for their use for personalized cancer management. In this review, we describe the current understanding of and advances in the clinical employment of CTCs. Although considered rare and fleeting, CTCs are now recognized as key players favoring the development of cancer metastasis and disease recurrence, particularly in malignant melanoma, lung, breast, and colorectal cancer patients. To date, the advancements in technology and the development of several successful approaches, also including immunomagnetic enrichment allow for a reliable and reproducible detection and characterization of CTCs. Those innovative methodologies improved the isolation, quantification, and characterization of CTCs from the blood of cancer patients, providing extremely useful evidence and new insights into the nature of the tumor, its epithelial/mesenchymal profile, and its potential resistance to therapy. In fact, in addition to their prognostic and predictive value, CTCs could serve as a valuable instrument for real-time monitoring of treatment response and disease recurrence, facilitating timely interventions and thus improving patient outcomes. However, despite their potential, several challenges hinder the widespread clinical utility of CTCs: (i) CTCs’ rarity and heterogeneity pose technical limitations in isolation and characterization, as well as significant hurdles in their clinical implementation; (ii) it is mandatory to standardize CTC detection methods, optimize the sample processing techniques, and integrate them with existing diagnostic modalities; and (iii) the need for the development of new techniques, such as single-cell analysis platforms, to enhance the sensitivity and specificity of CTC detection, thereby facilitating their integration into routine clinical practice. In conclusion, CTCs represent a potential extraordinary tool in cancer diagnostics and therapeutics, offering unprecedented opportunities for personalized medicine and precision oncology. Moreover, their ability to provide real-time insights into tumor biology, treatment response, and disease progression underlines a great potential for their clinical application to improve patients’ outcomes and advance our understanding of cancer biology. Full article
(This article belongs to the Special Issue The Biology of Circulating Tumor Cells 2.0)
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15 pages, 324 KiB  
Review
Clinical Significance of PD-L1 Status in Circulating Tumor Cells for Cancer Management during Immunotherapy
by Areti Strati, Panagiota Economopoulou, Evi Lianidou and Amanda Psyrri
Biomedicines 2023, 11(6), 1768; https://doi.org/10.3390/biomedicines11061768 - 20 Jun 2023
Cited by 3 | Viewed by 2573
Abstract
The approval of monoclonal antibodies against programmed death-ligand 1 (PD-L1) and programmed cell death protein (PD1) has changed the landscape of cancer treatment. To date, many immune checkpoint inhibitors (ICIs) have been approved by the FDA for the treatment of metastatic cancer as [...] Read more.
The approval of monoclonal antibodies against programmed death-ligand 1 (PD-L1) and programmed cell death protein (PD1) has changed the landscape of cancer treatment. To date, many immune checkpoint inhibitors (ICIs) have been approved by the FDA for the treatment of metastatic cancer as well as locally recurrent advanced cancer. However, immune-related adverse events (irAEs) of ICIs highlight the need for biomarker analysis with strong predictive value. Liquid biopsy is an important tool for clinical oncologists to monitor cancer patients and administer or change appropriate therapy. CTCs frequently express PD-L1, and this constitutes a clinically useful and non-invasive method to assess PD-L1 status in real-time. This review summarizes all the latest findings about the clinical significance of CTC for the management of cancer patients during the administration of immunotherapy and mainly focuses on the assessment of PD-L1 expression in CTCs. Full article
(This article belongs to the Special Issue The Biology of Circulating Tumor Cells 2.0)
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