Circulating Tumor Cells (CTCs) (2nd Edition)

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 106

Special Issue Editor


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Guest Editor
1. Division of Molecular Medicine, Department of Internal Medicine, The University of New Mexico Health Sciences Center, Albuquerque, NM 87120, USA
2. Department of Pathology, The University of New Mexico Health Sciences Center, Albuquerque, NM 87120, USA
3. 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,

This Special Issue is a continuation of our previous Special Issue, “Circulating Tumor Cells (CTCs)” (https://www.mdpi.com/journal/cancers/special_issues/cancers_CTCs).

The major cause of patient mortality in cancer is metastasis; however, our understanding of the metastatic cascade and mechanisms underlying this complex set of events remains limited. Cancer cells invade the surrounding tissue of primary or metastatic tumors, intravasate into lymphatic and blood vessels, disseminate to distant tissues, extravasate by adapting to the new microenvironment, and colonize these tissues. Because dissemination mostly occurs through the blood, circulating tumor cells (CTCs) are of paramount importance and one of the most promising areas of oncology research. CTCs might serve as a “liquid biopsy” as a better way to diagnose cancer patients compared to painful biopsies of the primary tumor and can represent a clinically useful tool to better reflect cancer progression and monitoring in the patient. The isolation, characterization, and interrogation of CTCs are hampered by their rarity and heterogeneity, either inherited from respective primary or metastatic tumors or as a result of CTC evolution in blood by genetic/epigenetic progression that may or may not lead to a fully metastatic-competent CTC. Significant technical challenges in the field also persist in regard to identifying and interrogating CTC heterogeneity, assessing CTC biomarkers of clinical utility, and comprehensively capturing these cells (usually, a ratio of one CTC per 106 leukocytes and 109 erythrocytes in one milliliter of blood). Finally, many studies have reported the clinical impact of enumerating CTCs, considering that CTC testing is being employed 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 the latest findings in CTC research and clinical implementation. Contributions outlining CTC discoveries in biological and clinical settings, CTC theoretical and preclinical models, CTC technologies and methods for their detection, and clinical findings applying CTC concepts are welcome.

Prof. Dr. Dario Marchetti
Guest Editor

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Keywords

  • liquid biopsy
  • metastatic biomarkers
  • CTCs isolation technologies
  • tumor heterogeneity
  • clinical CTC applications

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Published Papers (1 paper)

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Research

22 pages, 4086 KiB  
Article
Comprehensive Longitudinal Linear Mixed Modeling of CTCs Illuminates the Role of Trop2, EpCAM, and CD45 in CTC Clustering and Metastasis
by Seth D. Merkley, Huining Kang, Ursa Brown-Glaberman and Dario Marchetti
Cancers 2025, 17(16), 2717; https://doi.org/10.3390/cancers17162717 - 21 Aug 2025
Abstract
Background/Objectives: Breast cancer is the most commonly diagnosed cancer worldwide, with high rates of distant metastasis. While circulating tumor cells (CTCs) are the disseminatory units of metastasis and are indicative of a poor prognosis, CTC heterogeneity within individual patients, among breast cancer [...] Read more.
Background/Objectives: Breast cancer is the most commonly diagnosed cancer worldwide, with high rates of distant metastasis. While circulating tumor cells (CTCs) are the disseminatory units of metastasis and are indicative of a poor prognosis, CTC heterogeneity within individual patients, among breast cancer subtypes, and between primary and metastatic tumors within a patient obscures the relationship between CTCs and disease progression. EpCAM, its homolog Trop2, and a pan-Cytokeratin marker were evaluated to determine their contributions to CTC presence and clustering over the study period. We conducted a systematic longitudinal analysis of 51 breast cancer patients during the course of their treatment to deepen our understanding of CTC contributions to breast cancer progression. Methods: 272 total blood samples from 51 metastatic breast cancer (mBC) patients were included in the study. Patients received diverse treatment schedules based on discretion of the practicing oncologist. Patients were monitored from July 2020 to March 2023, with blood samples collected at scheduled care appointments. Nucleated cells were isolated, imaged, and analyzed using Rarecyte® technology, and statistical analysis was performed in R using the lmerTest and lme4 packages, as well as in Graphpad Prism version 10.4.1. Results: Both classical CTCs (DAPI+, EpCAM+, CK+, CD45– cells) and Trop2+ CTCs were detected in the blood of breast cancer patients. A high degree of correlation was found between CTC biomarkers, and CTC expression of EpCAM, Trop2, and the presence of CD45+ cells, all predicted cluster size, while Pan-CK did not. Furthermore, while analyses of biomarkers by receptor status revealed no significant differences among HR+, HER2+, and TNBC patients, longitudinal analysis found evidence for discrete trajectories of EpCAM, Trop2, and clustering between HR+ and HER2+ cancers after diagnosis of metastasis. Conclusions: Correlation and longitudinal analysis revealed that EpCAM+, Trop2+, and CD45+ cells were predictive of CTC cluster presence and size, and highlighted distinct trajectories of biomarker change over time between HR+ and HER2+ cancers following metastatic diagnosis. Full article
(This article belongs to the Special Issue Circulating Tumor Cells (CTCs) (2nd Edition))
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