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Cells
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Extracellular Vesicles and Exosomes: Novel Insight and Therapeutic Applications in...
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Extracellular Vesicles and Exosomes: Novel Insight and Therapeutic Applications in Cancer

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (20 April 2026) | Viewed by 6217

Special Issue Editors

Dr. Giusi Alberti

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Guest Editor
Department of Biomedicine, Neurosciences and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy
Interests: cancers
Dr. Celeste Caruso Bavisotto

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Guest Editor
Department of Biomedicine, Neurosciences and Advanced Diagnostic (BiND), Human Anatomy Section, University of Palermo, 90127 Palermo, Italy
Interests: cell differentiation; tissue homeostasis; organ remodeling; organ-on-chip; cell stress; chaperones; heat shock proteins; chaperonopathies; exosomes; glioblastoma
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Thanks to efforts made in recent years to uncover the factors involved in cancer progression, it is now clear that each factor has a unique imprint in cancer pathogenesis. Extracellular vesicles (EVs) and exosomes (Exos) are small structures involved in the regulation of biological processes through their cargo, which can comprise proteins, lipids, or nucleic acids. They are produced by tumor cells and function as a unique form of intercellular communication that can promote cell growth and survival, help shape the tumor microenvironment, and increase invasive and metastatic activity. However, the application of complex culture models to unravel the role of EVs and Exos in cancer research has not yet been popularized within EV research, given the difficulties that this type of culture presents, both technically and in terms of costs. This Special Issue will highlight the involvement of EVs and Exos in cancer physiology in order to identify potential applications in clinical oncology. The unique properties of EVs and Exos mean that they are promising tools in the therapeutic treatment of diseases, including neurodegenerative conditions and various types of cancer, highlighting the importance of 3D cultures in the study of EVs and Exos.

Dr. Giusi Alberti
Dr. Celeste Caruso Bavisotto
Guest Editors

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Keywords

  • extracellular vesicles (EVs)
  • exosomes (Exos)
  • proteins and miRNA
  • 2D-EVs and Exos
  • 3D-EVs and Exos
  • precision therapy
  • molecular mechanism
  • cancer physiology
  • oncology research

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Published Papers (3 papers)

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Review

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43 pages, 7705 KB  
Review
From CAR-T Cells to Exosome-Based Immunotherapy: Exploring the Frontiers of Cell-Free Targeted Cancer Therapeutics
by Alexandru Tîrziu, Florina Maria Bojin, Oana Isabella Gavriliuc, Cosmin Ioan Faur and Virgil Păunescu
Cells 2026, 15(1), 70; https://doi.org/10.3390/cells15010070 - 31 Dec 2025
Cited by 1 | Viewed by 2549
Abstract
Chimeric antigen receptor (CAR) cell therapies have revolutionized cancer immunotherapy by enabling targeted and potent antitumor immune responses. However, clinical challenges such as limited efficacy in solid tumors, severe toxicities including cytokine release syndrome (CRS), and manufacturing complexities restrict their broader use. Recently, [...] Read more.
Chimeric antigen receptor (CAR) cell therapies have revolutionized cancer immunotherapy by enabling targeted and potent antitumor immune responses. However, clinical challenges such as limited efficacy in solid tumors, severe toxicities including cytokine release syndrome (CRS), and manufacturing complexities restrict their broader use. Recently, CAR cell-derived exosomes (CAR-Exos) have emerged as promising cell-free therapeutic alternatives that retain the key antitumor functionalities of their parent cells while potentially overcoming the limitations of live cellular therapies. These nanoscale vesicles can deliver bioactive CAR molecules, cytotoxic proteins, and immunomodulatory cargo, enabling targeted tumor cell killing with reduced systemic toxicity and offering “off-the-shelf” applicability. This review comprehensively explores the biology, engineering, and therapeutic potential of CAR-Exos derived from T cells, natural killer (NK) cells, and other immune effectors. We discuss advances in isolation, characterization, and cargo profiling techniques, as well as preclinical and early clinical data supporting their application. Further, we address translational challenges including large-scale production, biodistribution, and immune evasion in tumor microenvironments. Combining cellular and exosomal CAR platforms holds promise to enhance efficacy and safety in cancer treatment, representing a frontier in targeted immunotherapy. Full article
(This article belongs to the Special Issue Extracellular Vesicles and Exosomes: Novel Insight and Therapeutic Applications in Cancer)
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16 pages, 1200 KB  
Review
Hsp60-Bearing Exosomes in Helicobacter pylori-Induced Gastric Tumorigenesis: A Pathomorphological and Therapeutical Overview
by Melania Ionelia Gratie, Olga Maria Manna, Salvatore Accomando, Giovanni Tomasello, Francesco Cappello and Alberto Fucarino
Cells 2025, 14(21), 1652; https://doi.org/10.3390/cells14211652 - 22 Oct 2025
Cited by 4 | Viewed by 1518
Abstract
Chronic infection with Helicobacter pylori is the leading environmental cause of gastric carcinogenesis, yet the molecular pathways remain incompletely defined. This review links H. pylori-derived outer membrane vesicles (OMVs) and host epithelial exosomes through their shared cargo of heat shock protein 60 [...] Read more.
Chronic infection with Helicobacter pylori is the leading environmental cause of gastric carcinogenesis, yet the molecular pathways remain incompletely defined. This review links H. pylori-derived outer membrane vesicles (OMVs) and host epithelial exosomes through their shared cargo of heat shock protein 60 (GroEL/Hsp60). We proposed the concept of the “muco-microbiotic layer” as a fifth, functionally distinct layer of the gastric wall, where bacterial and host extracellular vesicles (EVs) interact within the mucus–microbiota interface. In this compartment, OMVs carrying bacterial GroEL and exosomes containing human Hsp60 engage in bidirectional communication that may promote chronic inflammation and epithelial transformation, with putative participation of molecular mimicry. The high structural homology between microbial and human Hsp60 enables repeated immune exposure to trigger cross-reactive responses—potentially leading to autoimmune-driven tissue damage, immune tolerance, and immune evasion in pre-neoplastic lesions. This vesicular crosstalk aligns with the evolution from non-atrophic gastritis to atrophy, from intestinal metaplasia to dysplasia, and lastly adenocarcinoma. Therapeutically, targeting EV-mediated Hsp60/GroEL signaling might offer promising strategies: EV-based biomarkers for early detection, monoclonal antibodies against extracellular Hsp60/GroEL, modulation of vesicle release, and probiotic-derived nanovesicles to restore mucosal balance. Hence, recognizing the muco-microbiotic layer and its vesicle-mediated signaling provides a new framework for understanding the infection–inflammation–cancer axis and for developing diagnostic and therapeutic approaches in H. pylori-associated gastric cancer. Full article
(This article belongs to the Special Issue Extracellular Vesicles and Exosomes: Novel Insight and Therapeutic Applications in Cancer)
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Other

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18 pages, 3927 KB  
Systematic Review
Extracellular Vesicle Associated Proteomic Biomarkers in Breast Cancer: A Systematic Review and Meta-Analysis
by Nahad Al-Mahrouqi, Hasan Al-Sayegh, Shoaib Al-Zadjali and Aafaque Ahmad Khan
Cells 2026, 15(3), 231; https://doi.org/10.3390/cells15030231 - 26 Jan 2026
Cited by 2 | Viewed by 1067
Abstract
Breast cancer continues to be the most frequently diagnosed cancer among women worldwide and remains a leading cause of cancer-related mortality. Despite advances in imaging and biopsy-based approaches, current diagnostic methods are invasive, costly, and often insufficient to capture the molecular heterogeneity of [...] Read more.
Breast cancer continues to be the most frequently diagnosed cancer among women worldwide and remains a leading cause of cancer-related mortality. Despite advances in imaging and biopsy-based approaches, current diagnostic methods are invasive, costly, and often insufficient to capture the molecular heterogeneity of tumors. Extracellular vesicles (EVs) have emerged as promising non-invasive biomarkers owing to their role in intercellular communication and their enrichment with tumor-specific cargo. This study conducted a systematic review and meta-analysis of published literature to investigate proteomic alterations in EVs derived from breast cancer samples. From an initial 1097 records screened, four eligible studies were identified, reporting 628 differentially expressed proteins, of which 38 were consistently observed across multiple datasets. Functional enrichment analyses revealed predominant localization of these proteins to vesicle-associated compartments and significant involvement in biological processes related to cell growth, immune regulation, and tumor progression. Pathway analysis further highlighted integrin-mediated interactions, platelet activation, and hemostasis pathways as key molecular mechanisms represented within breast cancer EVs. Overall, the findings reveal a distinct EV proteomic signature in breast cancer that could support early detection and patient monitoring through minimally invasive testing. Future large-scale and standardized studies are needed to validate these candidate proteins and advance EV proteomics toward clinical application in breast cancer management. Full article
(This article belongs to the Special Issue Extracellular Vesicles and Exosomes: Novel Insight and Therapeutic Applications in Cancer)
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