@article{2228a7f304da4c2eb864bbb532905f8f,
title = "Targeting Epstein-Barr Virus in Nasopharyngeal Carcinoma",
abstract = "Nasopharyngeal carcinoma (NPC) is consistently associated with Epstein-Barr virus (EBV) infection in regions in which it is endemic, including Southern China and Southeast Asia. The high mortality rates of NPC patients with advanced and recurrent disease highlight the urgent need for effective treatments. While recent genomic studies have revealed few druggable targets, the unique interaction between the EBV infection and host cells in NPC strongly implies that targeting EBV may be an efficient approach to cure this virus-associated cancer. Key features of EBV-associated NPC are the persistence of an episomal EBV genome and the requirement for multiple viral latent gene products to enable malignant transformation. Many translational studies have been conducted to exploit these unique features to develop pharmaceutical agents and therapeutic strategies that target EBV latent proteins and induce lytic reactivation in NPC. In particular, inhibitors of the EBV latent protein EBNA1 have been intensively explored, because of this protein's essential roles in maintaining EBV latency and viral genome replication in NPC cells. In addition, recent advances in chemical bioengineering are driving the development of therapeutic agents targeting the critical functional regions of EBNA1. Promising therapeutic effects of the resulting EBNA1-specific inhibitors have been shown in EBV-positive NPC tumors. The efficacy of multiple classes of EBV lytic inducers for NPC cytolytic therapy has also been long investigated. However, the lytic-induction efficiency of these compounds varies among different EBV-positive NPC models in a cell-context-dependent manner. In each tumor, NPC cells can evolve and acquire somatic changes to maintain EBV latency during cancer progression. Unfortunately, the poor understanding of the cellular mechanisms regulating EBV latency-to-lytic switching in NPC cells limits the clinical application of EBV cytolytic treatment. In this review, we discuss the potential approaches for improvement of the above-mentioned EBV-targeting strategies.",
keywords = "BZLF1, cytolytic therapy, EBNA1, Epstein-Barr virus, LMP1, nasopharyngeal carcinoma",
author = "Hau, {Pok Man} and Lung, {Hong Lok} and Man Wu and Tsang, {Chi Man} and Ka-Leung Wong and Mak, {Nai Ki} and Lo, {Kwok Wai}",
note = "Funding Information: We thank Core Utilities of Cancer Genome and Pathobiology of the Faculty of Medicine, The Chinese University of Hong Kong for providing support for our studies. Funding. KL was supported by the Research Grant Council, Hong Kong (Theme-based Research Scheme ?T12-401/13-R; Collaborative Research Fund?C4001-18GF, C7027-16G; General Research Fund?14104415, 14138016, and 14117316), the Focused Innovations Scheme and Faculty Strategic Research (4620513) of the Faculty of Medicine, and the VC's One-off Discretionary Fund (VCF2014017, VCF2014015) of the Chinese University of Hong Kong. CT was supported by the General Research Fund (17110315 and 17111516) of the Research Grant Council, the Health and Medical Research Fund (05162386 and 13142201), and the NSFC/RGC Joint Research Scheme?N_HKU735/18. HL, K-LW, and NM were supported by the Hong Kong Baptist University (RC-IRMS/16-17/CHE, RC-ICRS/16-17/02A-BOL, RC-IRMS/16-17/01, and MPCF-002-2018/19) and Hong Kong Research Grants Council (HKBU 20301615 and 12300117, the NPC Area of Excellence, AoE/M 06/08 Center for Nasopharyngeal Carcinoma Research, and Research Grants Council Collaborative Research Fund Scheme C4001-18GF). Funding Information: KL was supported by the Research Grant Council, Hong Kong (Theme-based Research Scheme —T12-401/13-R; Collaborative Research Fund—C4001-18GF, C7027-16G; General Research Fund−14104415, 14138016, and 14117316), the Focused Innovations Scheme and Faculty Strategic Research (4620513) of the Faculty of Medicine, and the VC{\textquoteright}s One-off Discretionary Fund (VCF2014017, VCF2014015) of the Chinese University of Hong Kong. CT was supported by the General Research Fund (17110315 and 17111516) of the Research Grant Council, the Health and Medical Research Fund (05162386 and 13142201), and the NSFC/RGC Joint Research Scheme— N_HKU735/18. HL, K-LW, and NM were supported by the Hong Kong Baptist University (RC-IRMS/16-17/CHE, RC-ICRS/16-17/02A-BOL, RC-IRMS/16-17/01, and MPCF-002-2018/19) and Hong Kong Research Grants Council (HKBU 20301615 and 12300117, the NPC Area of Excellence, AoE/M 06/08 Center for Nasopharyngeal Carcinoma Research, and Research Grants Council Collaborative Research Fund Scheme C4001-18GF).",
year = "2020",
month = may,
day = "14",
doi = "10.3389/fonc.2020.00600",
language = "English",
volume = "10",
journal = "Frontiers in Oncology",
issn = "2234-943X",
publisher = "Frontiers Media S.A.",
}