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Epstein-Barr Virus-Associated Cancers: From Pathogenesis to Treatment (2nd Edition)

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Infectious Agents and Cancer".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 3224

Special Issue Editor


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Guest Editor
Department of Anatomical and Cellular Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
Interests: molecular genetics of nasopharyngeal carcinoma (NPC); NPC genomics; roles of EBV in NPC tumorigenesis; new therapeutic approaches for NPC; tumor microenvironment and cancer stem-like cells in NPC
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Special Issue Information

Dear Colleagues,

This Special Issue is the second edition of the Special Issue Epstein-Barr Virus-Associated Cancers: From Pathogenesis to Treatment.

After almost 60 years of research on the Epstein–Barr virus (EBV), we are still grappling with its precise role in oncogenesis and with the ways in which this can be exploited to improve the clinical management of EBV-associated cancers. There is still much to learn about the natural history of EBV infection and how the virus interacts with different risk factors to drive the development of cancer. This Special Issue aims at providing an up-to-date assessment of the current status of our understanding of EBV’s contribution to virus-associated lymphomas and carcinomas and of the ways in which this knowledge impacts the diagnosis and treatment of these cancers. Original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: (i) the role of EBV in the development of different tumours, including the contribution of EBV latent and lytic proteins; (ii) the interaction of different co-factors and the ways in which these work in concert with EBV to drive oncogenesis; (iii) the impact of EBV on the tumour microenvironment; (iv) the use of EBV as a biomarker in tumour diagnosis and prognosis; (v) current and future approaches to treating EBV-associated cancers, including immunotherapy and the targeting of individual EBV proteins; and (vi) the potential of both prophylactic and therapeutic vaccination.

I look forward to receiving your contributions.

Prof. Dr. Kwok-Wai Lo
Guest Editor

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Keywords

  • EBV
  • lymphomas
  • Burkitt lymphoma
  • Hodgkin lymphoma
  • NK/T cell lymphoma
  • nasopharyngeal carcinoma
  • gastric cancer
  • biomarkers
  • immunotherapy
  • targeted therapy

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Published Papers (3 papers)

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Research

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19 pages, 1513 KB  
Article
SFK Inhibition Suppresses EBV-Encoded BART miRNAs and Induces Apoptosis in EBV-Positive Gastric Epithelial Cells
by Yuxin Liu, Zolzaya Tumurgan, Aung Phyo Wai, Moushumi Akter, Afifah Fatimah Azzahra Ahmad Wadi, Yoichi Mizukami, Masami Wada, Shunpei Okada, Daisuke Niino, Takayuki Murata, Hisashi Iizasa and Hironori Yoshiyama
Cancers 2026, 18(7), 1082; https://doi.org/10.3390/cancers18071082 - 26 Mar 2026
Viewed by 614
Abstract
Background/Objectives: Epstein–Barr virus (EBV) is associated with a subset of gastric carcinomas characterized by latency programs that promote survival of infected cells. EBV-encoded BamH I A rightward transcript (BART) microRNAs contribute to apoptosis resistance in infected epithelial cells. This study investigated whether [...] Read more.
Background/Objectives: Epstein–Barr virus (EBV) is associated with a subset of gastric carcinomas characterized by latency programs that promote survival of infected cells. EBV-encoded BamH I A rightward transcript (BART) microRNAs contribute to apoptosis resistance in infected epithelial cells. This study investigated whether dasatinib, a Src family kinase (SFK) inhibitor, selectively targets EBV-positive gastric epithelial cells and examined the molecular mechanisms underlying this effect. Methods: EBV-positive and EBV-negative gastric epithelial cell models were analyzed to evaluate cell viability, apoptosis induction, signaling pathways, and viral gene regulation. BART miRNA expression was quantified by RT-qPCR, and promoter activity was examined using luciferase reporter assays. Downstream target gene expression was analyzed at both the transcript and protein levels. Recombinant EBV lacking BZLF1 or LMP2A was used to assess the contributions of lytic activation and LMP2A-associated signaling. Results: Dasatinib preferentially reduced viability and induced apoptosis in EBV-positive gastric epithelial cells compared with EBV-negative counterparts. Treatment suppressed phosphorylation of Src and ERK and reduced expression of the anti-apoptotic proteins BCL-xL and MCL1. Apoptosis was also observed in cells infected with LMP2A-deficient EBV, suggesting that the effect cannot be fully explained by inhibition of LMP2A-associated signaling. Dasatinib inhibited BART miRNA promoter activity and reduced pri-, pre-, and mature miR-BART levels, accompanied by increased expression of pro-apoptotic target genes including CASZ1a, OCT1, ARID2, TP53INP1, and DAB2. In parallel, dasatinib suppressed BZLF1 promoter activity without evidence of lytic reactivation. Conclusions: Dasatinib promotes apoptosis in EBV-positive gastric epithelial cells in association with coordinated suppression of SFK signaling and EBV-encoded BART miRNA expression, accompanied by derepression of pro-apoptotic cellular genes. These findings reveal a previously underappreciated vulnerability of EBV-positive epithelial cells and suggest that targeting host kinase signaling pathways that regulate viral microRNAs may represent a potential therapeutic strategy for EBV-associated malignancies. Full article
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18 pages, 175342 KB  
Article
The EBV-Positive Tumor Methylome Is Distinct from EBV-Negative in Diffuse Large B-Cell Lymphoma
by Ashley K. Volaric, Ramiro Barrantes-Reynolds, Karine Sahakyan, Yuri Fedoriw and Seth Frietze
Cancers 2025, 17(18), 2994; https://doi.org/10.3390/cancers17182994 - 13 Sep 2025
Cited by 1 | Viewed by 1461
Abstract
Backgrounds: Epstein–Barr virus (EBV) is implicated in the pathogenesis of different B-cell lymphomas and lymphoproliferative disorders, including diffuse large B-cell lymphoma (DLBCL) arising in immunodeficiency settings. Despite its clinical significance, the mechanisms of EBV-mediated lymphomagenesis across different disease subtypes remain poorly understood. [...] Read more.
Backgrounds: Epstein–Barr virus (EBV) is implicated in the pathogenesis of different B-cell lymphomas and lymphoproliferative disorders, including diffuse large B-cell lymphoma (DLBCL) arising in immunodeficiency settings. Despite its clinical significance, the mechanisms of EBV-mediated lymphomagenesis across different disease subtypes remain poorly understood. Global DNA methylation profiling can provide insight into tumor heterogeneity and disease mechanisms. Methods: To further characterize the underlying biology of EBV(+) DLBCL, we performed a global methylome analysis of a cohort of EBV(+)/(−) DLBCL. Illumina MethylationEPIC array data were generated from a curated set of DLBCL tissue samples (n = 43) from a rural patient population with defined EBV status and immunodeficiency background. Differential methylation analyses were conducted using linear mixed models to identify significant methylation changes associated with EBV status. Results: Principle component analysis (PCA) and probe-level comparisons revealed a distinct, globally hypermethylated DNA methylome in EBV(+) DLBCL compared to EBV(−) cases, and an overall hypomethylated profile in all DLBCL relative to control tissues. We identified a total of 117,334 differentially methylated probes mapping to 1557 cancer-associated genes in EBV(+) versus EBV(−) DLBCL, and 330,872 probes mapping to 4230 cancer-associated genes in all DLBCL versus controls. Pathway enrichment analysis highlighted distinct biological processes in EBV(+) DLBCL, including P53 feedback loops (hypermethylated genes) and MAPK signaling (hypomethylated genes). Conclusions: These findings demonstrate that EBV(+) DLBCL is epigenetically distinct from EBV(−) disease, with alterations that may contribute to clinical heterogeneity and potentially serve as biomarkers for disease classification and therapeutic targeting. Full article
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Review

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18 pages, 2160 KB  
Review
Relevance of Epstein-Barr Virus (EBV) miRNAs in EBV-Infected B Cells and B-Cell Lymphomas
by Nohora Juliana Rueda-Forero, Joost Kluiver, Marije Koning, Anke van den Berg and Arjan Diepstra
Cancers 2026, 18(6), 962; https://doi.org/10.3390/cancers18060962 - 16 Mar 2026
Cited by 1 | Viewed by 687
Abstract
Viral infection is a critical early event in Epstein–Barr virus (EBV)-positive B-cell lymphomas. While latent EBV proteins are known to promote cancer development, the role of EBV-encoded microRNAs (miRNAs) is not yet clear. These miRNAs are reported to regulate viral persistence, immune evasion, [...] Read more.
Viral infection is a critical early event in Epstein–Barr virus (EBV)-positive B-cell lymphomas. While latent EBV proteins are known to promote cancer development, the role of EBV-encoded microRNAs (miRNAs) is not yet clear. These miRNAs are reported to regulate viral persistence, immune evasion, B-cell survival, and growth. This review compiles evidence on the role of EBV miRNAs in B cells and B-cell lymphomas, including their known target genes, and their effects on cancer-related pathways. By combining profiling studies and results from laboratory models, we highlight how EBV miRNAs might contribute to lymphoma development. Overall, this review provides a comprehensive overview of the biology of EBV-positive B-cell lymphoma, and current knowledge supports a critical role for EBV miRNAs in B cell transformation. Full article
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