ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2021
EBNA1 inhibitors have potent and selective antitumor activity in xenograft models of Epstein-Barr virus-associated gastric cancer.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Design and Optimization of Benzoic Acid Inhibitors Targeting the EBNA1 DNA-Binding Interface.ACS medicinal chemistry letters · 2026Article
- VK-2019 enhances gemcitabine's antitumor activity in EBV-positive nasopharyngeal carcinoma by upregulating PRODH expression.Cell death discovery · 2026Article
- Targeting EBV-associated gastric cancer by lytic induction therapy with nanatinostat.Tumour virus research · 2026Article
- EBNA1 inhibitors reveal CDC7 and POU2F1 as direct functional targets in EBV epithelial cancers.mBio · 2026Article
- EBNA1BP2 (EBP2) promotes the progression of hepatocellular carcinoma through upregulating the expression of MCM8 and HMGB1.Cell death & disease · 2026Article
- Nanobodies targeting the Epstein-Barr virus EBNA1 DNA binding domain inhibit tumor growth.Journal of nanobiotechnology · 2026Article
- Epstein-Barr virus pathogenesis and emerging control strategies.Nature reviews. Microbiology · 2025Review
- The case for targeting latent and lytic Epstein-Barr virus infection in multiple sclerosis.Brain : a journal of neurology · 2025Review
- Causal association between EBV and gastritis, gastric cancer, and gastric ulcer: a two-sample Mendelian randomization study.Scientific reports · 2025Article
- Research landmarks on the 60th anniversary of Epstein-Barr virus.Science China. Life sciences · 2025Review
- Epstein-Barr virus-infected nasopharyngeal carcinoma therapeutics: oncoprotein targets and clinical implications.Medical oncology (Northwood, London, England) · 2025Review
- Review
- Article
- Momordica anti-HIV protein MAP30 abrogates the Epstein-Barr virus nuclear antigen 1 dependent functions in host cells.Heliyon · 2023Article
- EBNA1 Inhibitors Block Proliferation of Spontaneous Lymphoblastoid Cell Lines From Patients With Multiple Sclerosis and Healthy Controls.Neurology(R) neuroimmunology & neuroinflammation · 2023Article
- Review
- Pathogenesis and therapeutic implications of EBV-associated epithelial cancers.Frontiers in oncology · 2023Review
- Review
- Therapeutic approaches to Epstein-Barr virus cancers.Current opinion in virology · 2022Review
- EBV-associated diseases: Current therapeutics and emerging technologies.Frontiers in immunology · 2022Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
aimsEpstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is the most common EBV-associated cancer and accounts for ~ 10% of all gastric cancers (GC). Epstein-Barr virus nuclear antigen 1 (EBNA1), which is critical for the replication and maintenance of the EBV latent genome, is consistently expressed in all EBVaGC tumors. We previously developed small molecule inhibitors of EBNA1. In this study, we investigated the efficacy and selectivity of an EBNA1 inhibitor in cell-based and animal xenograft models of EBV-positive and EBV-negative gastric carcinoma.
methodsWe tested the potency of an EBNA1 inhibitor, VK-1727, in vitro and in xenograft studies, using EBV-positive (SNU719 and YCCEL1) and EBV-negative (AGS and MKN74) GC cell lines. After treatment, we analyzed cell viability, proliferation, and RNA expression of EBV genes by RT-qPCR.
resultsTreatment with VK-1727 selectively inhibits cell cycle progression and proliferation in vitro. In animal studies, treatment with an EBNA1 inhibitor resulted in a significant dose-dependent decrease in tumor growth in EBVaGC xenograft models, but not in EBV-negative GC xenograft studies. Gene expression analysis revealed that short term treatment in cell culture tended towards viral gene activation, while long-term treatment in animal xenografts showed a significant decrease in viral gene expression.
conclusionsEBNA1 inhibitors are potent and selective inhibitors of cell growth in tissue culture and animal models of EBV-positive GC. Long-term treatment with EBNA1 inhibitors may lead to loss of EBV in mouse xenografts. These results suggest that pharmacological targeting of EBNA1 may be an effective strategy to treat patients with EBVaGC.
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