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The Role of Extracellular Vesicles in Cancer Diagnosis and Therapy, 2nd Edition

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

Deadline for manuscript submissions: 30 August 2025 | Viewed by 7026

Special Issue Editor

Dr. Nils Ludwig

E-Mail Website
Guest Editor
Department of Cranio- and Maxillofacial Surgery, Hospital of the University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
Interests: extracellular vesicles; exosomes; cell-to-cell communication; head and neck cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue titled “The Role of Exosomes in Cancer Diagnosis and Therapy”. Due to the extensive research in recent years, small extracellular vesicles (sEVs), also known as exosomes, are now considered major contributors to intercellular communication in health and disease. Small extracellular vesicles carry a complex cargo composition consisting of proteins, nucleic acids, and lipids, and it has been shown that components of sEVs are biologically active and induce effects in recipient cells. These characteristics of sEVs motivated researchers worldwide to further explore their biology under physiological as well as pathophysiological conditions, and especially tumor-cell-derived sEVs have been extensively studied. Research shows that tumor-cell-derived sEVs promote tumor progression by local and systemic effects, and functionally contribute to malignant processes such as metastasis, immunosuppression, angiogenesis, and drug resistance. Besides their functional effects in the tumor microenvironment, sEVs have been shown to serve as attractive biomarkers or could even be utilized for sEV-based nanotherapeutic approaches.

The important versatile roles of sEVs in cancer motivated us to serve as Guest Editors of this Special Issue and create a collection of articles fully dedicated to sEV biology. We aim to focus this Special Issue on the molecular aspects of sEVs by shifting the main emphasis on the use of sEVs for cancer diagnosis as well as using sEVs as cancer therapeutics. We welcome any articles investigating sEVs as cancer biomarkers, nanotherapeutics or even how sEVs promote drug resistance in cancer.

We hope that your contribution to this Special Issue will be a positive experience for you and for the sEV research community. We invite you to contribute your research to this Special Issue on “The Role of Extracellular Vesicles in Cancer Diagnosis and Therapy 2.0”.

Dr. Nils Ludwig
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

  • extracellular vesicles
  • exosomes
  • intercellular communication
  • liquid biopsy
  • cancer therapeutics
  • nanotherapeutics

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Related Special Issue

Published Papers (3 papers)

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Research

18 pages, 2199 KiB  
Article
Exosomal CD40, CD25, and Serum CA19-9 as Combinatory Novel Liquid Biopsy Biomarker for the Diagnosis and Prognosis of Patients with Pancreatic Ductal Adenocarcinoma
by Paul David, Dina Kouhestani, Frederik J. Hansen, Sushmita Paul, Franziska Czubayko, Alara Karabiber, Nadine Weisel, Bettina Klösch, Susanne Merkel, Jan Ole-Baur, Andreas Gießl, Jan Van Deun, Julio Vera, Anke Mittelstädt and Georg F. Weber
Int. J. Mol. Sci. 2025, 26(4), 1500; https://doi.org/10.3390/ijms26041500 - 11 Feb 2025
Cited by 1 | Viewed by 1183
Abstract
The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is largely due to several challenges, such as late diagnosis, early metastasis, limited response to chemotherapy, aggressive tumor biology, and high rates of tumor recurrence. Therefore, the development of a non-invasive and effective method for [...] Read more.
The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is largely due to several challenges, such as late diagnosis, early metastasis, limited response to chemotherapy, aggressive tumor biology, and high rates of tumor recurrence. Therefore, the development of a non-invasive and effective method for early detection of PDAC is crucial to improving patient outcomes. Continued research and exploration in this area are essential to enhance early detection methods and ultimately improve the prognosis for individuals with PDAC. In this study, we examined 37 exosomal surface proteins through a multiplex flow cytometry test on peripheral plasma samples from a group of 51 clinical control individuals (including healthy volunteers and non-cancer patients (Cholecystectomy, Hernia, healthy volunteers)), 21 pancreatitis, and 48 patients diagnosed with PDAC. Our research findings revealed that the level of exosomal CD40 expression is significantly lower in patients with PDAC and pancreatitis compared to non-cancer patients (p < 0.0001). Additionally, pancreatitis patients exhibited higher levels of exosomal CD25 expression than PDAC patients (p = 0.0104). PDAC patients with higher exo-CD40 had worse survival than patients with lower exo-CD40 (p = 0.0035). Similarly, PDAC patients with higher exo-CD25 showed worse survival in comparison to patients with lower exo-CD25 (p = 0.04). Statistical analysis revealed that exosomal CD40 achieved an AUC of 0.827 in distinguishing PDAC from clinical controls. Combining exo-CD40 along with exo-CD25 and CA19-9 discriminated PDAC patients from clinical controls with an AUC of 0.92. Exo-CD40 and exo-CD25 proteins found in exosomes isolated from plasma can serve as excellent non-invasive biomarkers for the early diagnosis of PDAC. Further larger scale studies are needed to validate combined exo-CD40 and exo-CD25 as a diagnostic tool for the identification of PDAC patients through non-invasive liquid biopsy. Full article
(This article belongs to the Special Issue The Role of Extracellular Vesicles in Cancer Diagnosis and Therapy, 2nd Edition)
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25 pages, 16209 KiB  
Article
The Effect of Ionising Radiation on the Properties of Tumour-Derived Exosomes and Their Ability to Modify the Biology of Non-Irradiated Breast Cancer Cells—An In Vitro Study
by Michał Stefan Lach, Joanna Patrycja Wróblewska, Marcin Michalak, Bartłomiej Budny, Elżbieta Wrotkowska and Wiktoria Maria Suchorska
Int. J. Mol. Sci. 2025, 26(1), 376; https://doi.org/10.3390/ijms26010376 - 4 Jan 2025
Cited by 1 | Viewed by 3488
Abstract
The vast majority of breast cancer patients require radiotherapy but some of them will develop local recurrences and potentially metastases in the future. Recent data show that exosomal cargo is essential in these processes. Thus, we investigated the influence of ionising radiation on [...] Read more.
The vast majority of breast cancer patients require radiotherapy but some of them will develop local recurrences and potentially metastases in the future. Recent data show that exosomal cargo is essential in these processes. Thus, we investigated the influence of ionising radiation on exosome properties and their ability to modify the sensitivity and biology of non-irradiated cells. Exosomes were isolated from breast cancer cell lines (MDA-MB-231, MCF7, and SKBR3) irradiated with 2 Gy (Exo 2 Gy) or no irradiation (Exo 0 Gy). Despite some differences in their molecular profiles, they did not affect cell viability, proliferation, cell cycle phase distribution, and radioresistance; however, both populations showed the ability to modify cell migration and invasion potential, as confirmed by the downregulation of β-catenin, which is responsible for maintaining the epithelial phenotype. Interestingly, exosomes from irradiated BCa cells were more actively deposited in the endothelial cells (EA.hy926). Furthermore, exosomes tend to lower the expression of CD31, which is responsible for maintaining intact vascularity. This preliminary study demonstrates the vital role of exosomes and their altered profile due to irradiation in the pathobiology of breast cancer. Full article
(This article belongs to the Special Issue The Role of Extracellular Vesicles in Cancer Diagnosis and Therapy, 2nd Edition)
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14 pages, 1987 KiB  
Communication
Phenotypic Biomarkers of Aqueous Extracellular Vesicles from Retinoblastoma Eyes
by Anne Amacker, Chen-Ching Peng, Nan Jiang, Shreya Sirivolu, Nikki Higa, Kevin Stachelek, Bibiana Reiser, Peter Kuhn, David Cobrinik, Paolo Neviani, Jesse L. Berry, Tijana Jovanovic-Talisman and Liya Xu
Int. J. Mol. Sci. 2024, 25(21), 11660; https://doi.org/10.3390/ijms252111660 - 30 Oct 2024
Cited by 2 | Viewed by 1507
Abstract
Recent advancements in aqueous humor (AH) cell-free DNA (cfDNA) genomics have opened new avenues for ex vivo molecular profiling of retinoblastoma (RB), the most common pediatric intraocular malignancy, where biopsy is typically prohibited. While these insights offer a genetic blueprint of the tumor, [...] Read more.
Recent advancements in aqueous humor (AH) cell-free DNA (cfDNA) genomics have opened new avenues for ex vivo molecular profiling of retinoblastoma (RB), the most common pediatric intraocular malignancy, where biopsy is typically prohibited. While these insights offer a genetic blueprint of the tumor, they lack multi-omic molecular phenotyping, which is essential for understanding the functional state. Extracellular vesicles (EVs), naturally present in AH, are promising by offering time-resolved phenotypic information. We employed multiplex bead-based flow cytometry and Single Extracellular Vesicle Nanoscopy (SEVEN) to analyze EV phenotypes in AH from a cohort of five RB, with three uveal melanoma (UM) and two age-matched glaucoma (GLC) samples serving as controls. The studies identified CD133-enriched EVs uniquely in RB AH, absent in both GLC and UM AH. This was corroborated by further analysis of five RB cell lines, including two commercial (Y79, Weri) and three in-house developed lines, confirming CD133 enrichment and supporting its role as an RB-specific EV marker. Single-vesicle analysis demonstrated a strong association of CD133 with CD81 and CD63, with minimal CD9 presence. These results, validated through complementary techniques, position CD133 as a critical marker in RB-derived EVs, paving the way for enhanced multi-omic RB characterization and potential advancements in clinical diagnostics. Full article
(This article belongs to the Special Issue The Role of Extracellular Vesicles in Cancer Diagnosis and Therapy, 2nd Edition)
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