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Targeting EBV-associated gastric cancer by lytic induction therapy with nanatinostat.

Created on 28 Jun 2026

Authors

Man Wu, Shin Yee Hui, Andrew Skora, Yuk Yu Chan, Grace Tin-Yun Chung, Lili Li, Qian Tao, Dajiang Guo, Christopher W Dawson, Lawrence S Young, Chi Man Tsang, Ayman El-Guindy, Kwok Wai Lo

Published in

Tumour virus research. Pages 200346. Jun 27, 2026. Epub Jun 27, 2026.

Abstract

Latent Epstein-Barr virus (EBV) infection is associated with multiple lymphoid and epithelial cancers in humans. Targeting EBV through lytic induction therapy represents a potential strategy for treating virus-associated malignancies, such as EBV-associated gastric cancer (EBVaGC). Despite its classification as a distinct gastric cancer subtype, precision therapeutic strategies for EBVaGC remain vastly underexplored. In a recent clinical study, the combination of an orally administered histone deacetylase (HDAC) inhibitor, nanatinostat (NSTAT) with valganciclovir (GCV), showed promise as a lytic induction therapy for EBV-positive lymphoma. In this study, we evaluated the activity of NSTAT to induce EBV lytic reactivation and the therapeutic efficacy of NSTAT-based lytic induction therapy in two representative EBVaGC cell lines in vitro and in vivo. NSTAT efficiently induced the expression of EBV immediate-early, early and late genes in EBVaGC cells. In addition, NSTAT treatment also promoted global histone acetylation and suppressed c-MYC and BCL2 expression, leading to cell cycle arrest and cell death in the EBVaGC tumor cells. Importantly, this study demonstrated the potent antitumor efficacy and safety of combined NSTAT and GCV treatment in both in vitro and in vivo preclinical EBVaGC models.

PMID:
42364907
Bibliographic data and abstract were imported from PubMed on 28 Jun 2026.

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