{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:04:27Z","timestamp":1792029867863,"version":"4.4.0"},"reference-count":176,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,2]],"date-time":"2020-08-02T00:00:00Z","timestamp":1596326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["16150472"],"award-info":[{"award-number":["16150472"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005847","name":"Health and Medical Research Fund","doi-asserted-by":"publisher","award":["17160712"],"award-info":[{"award-number":["17160712"]}],"id":[{"id":"10.13039\/501100005847","id-type":"DOI","asserted-by":"publisher"}]},{"name":"undefined  &lt;span style=&quot;color:gray;font-size:10px;&quot;&gt;undefined&lt;\/span&gt;","award":["RGC Collaborative Research Fund (CRF) Scheme Grant # C4001-18G"],"award-info":[{"award-number":["RGC Collaborative Research Fund (CRF) Scheme Grant # C4001-18G"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Epstein\u2013Barr virus (EBV) lytic induction therapy is an emerging virus-targeted therapeutic approach that exploits the presence of EBV in tumor cells to confer specific killing effects against EBV-associated malignancies. Efforts have been made in the past years to uncover the mechanisms of EBV latent-lytic switch and discover different classes of chemical compounds that can reactivate the EBV lytic cycle. Despite the growing list of compounds showing potential to be used in the lytic induction therapy, only a few are being tested in clinical trials, with varying degrees of success. This review will summarize the current knowledge on EBV lytic reactivation, the major hurdles of translating the lytic induction therapy into clinical settings, and highlight some potential strategies in the future development of this therapy for EBV-related lymphoid and epithelial malignancies.<\/jats:p>","DOI":"10.3390\/cancers12082142","type":"journal-article","created":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T06:16:47Z","timestamp":1596435407000},"page":"2142","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Lytic Induction Therapy against Epstein\u2013Barr Virus-Associated Malignancies: Past, Present, and Future"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1792-247X","authenticated-orcid":false,"given":"Stephanie Pei Tung","family":"Yiu","sequence":"first","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9402-426X","authenticated-orcid":false,"given":"Mike","family":"Dorothea","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwai Fung","family":"Hui","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1089-5325","authenticated-orcid":false,"given":"Alan Kwok Shing","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1128\/CMR.00044-10","article-title":"Progress and problems in understanding and managing primary Epstein-Barr virus infections","volume":"24","author":"Odumade","year":"2011","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","first-page":"149","article-title":"Epstein-Barr virus infection and human malignancies","volume":"82","author":"Niedobitek","year":"2001","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1136\/jcp.2006.044586","article-title":"Epstein Barr virus-associated tumours: An update for the attention of the working pathologist","volume":"60","author":"Delecluse","year":"2007","journal-title":"J. Clin. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1002\/ijc.32049","article-title":"High risk Epstein-Barr virus variants characterized by distinct polymorphisms in the EBER locus are strongly associated with nasopharyngeal carcinoma","volume":"144","author":"Hui","year":"2019","journal-title":"Int. J. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1056\/NEJMra032015","article-title":"Persistence of the Epstein-Barr virus and the origins of associated lymphomas","volume":"350","author":"Gross","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1007\/s11864-013-0231-y","article-title":"EBV-related lymphomas: New approaches to treatment","volume":"14","author":"Kanakry","year":"2013","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5122","DOI":"10.1038\/sj.onc.1206548","article-title":"Virally targeted therapies for EBV-associated malignancies","volume":"22","author":"Israel","year":"2003","journal-title":"Oncogene"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.7150\/ijbs.16564","article-title":"Epstein-Barr virus lytic reactivation regulation and its pathogenic role in carcinogenesis","volume":"12","author":"Li","year":"2016","journal-title":"Int. J. Biol Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7892","DOI":"10.1128\/JVI.00379-10","article-title":"Differential expression of the miR-200 family microRNAs in epithelial and B cells and regulation of Epstein-Barr virus reactivation by the miR-200 family member miR-429","volume":"84","author":"Lin","year":"2010","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10329","DOI":"10.1128\/JVI.00923-10","article-title":"Cellular microRNAs 200b and 429 regulate the Epstein-Barr virus switch between latency and lytic replication","volume":"84","author":"Iempridee","year":"2010","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Chen, Y., Fachko, D., Ivanov, N.S., Skinner, C.M., and Skalsky, R.L. (2019). Epstein-Barr virus microRNAs regulate B cell receptor signal transduction and lytic reactivation. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007535"},{"key":"ref_12","first-page":"5274","article-title":"The \u201cbystander effect\u201d: Tumor regression when a fraction of the tumor mass is genetically modified","volume":"53","author":"Freeman","year":"1993","journal-title":"Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4534","DOI":"10.1128\/JVI.02487-09","article-title":"The Epstein-Barr virus (EBV)-encoded protein kinase, EBV-PK, but not the thymidine kinase (EBV-TK), is required for ganciclovir and acyclovir inhibition of lytic viral production","volume":"84","author":"Meng","year":"2010","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3389\/fonc.2019.00081","article-title":"Viral-Targeted Strategies Against EBV-Associated Lymphoproliferative Diseases","volume":"9","author":"Hui","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"721","DOI":"10.2147\/TCRM.S47434","article-title":"Therapeutic implications of Epstein-Barr virus infection for the treatment of nasopharyngeal carcinoma","volume":"10","author":"Hutajulu","year":"2014","journal-title":"Ther. Clin. Risk Manag."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5061","DOI":"10.1158\/1078-0432.CCR-12-0574","article-title":"Cytolytic virus activation therapy for Epstein-Barr virus-driven tumors","volume":"18","author":"Wildeman","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1128\/JVI.78.4.1893-1902.2004","article-title":"Lytic induction therapy for Epstein-Barr virus-positive B-cell lymphomas","volume":"78","author":"Feng","year":"2004","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1111\/cas.13634","article-title":"Therapies based on targeting Epstein-Barr virus lytic replication for EBV-associated malignancies","volume":"109","author":"Li","year":"2018","journal-title":"Cancer Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/ijc.29698","article-title":"Inhibition of class I histone deacetylases by romidepsin potently induces Epstein-Barr virus lytic cycle and mediates enhanced cell death with ganciclovir","volume":"138","author":"Hui","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1099\/vir.0.83533-0","article-title":"Essential role of PKCdelta in histone deacetylase inhibitor-induced Epstein-Barr virus reactivation in nasopharyngeal carcinoma cells","volume":"89","author":"Lee","year":"2008","journal-title":"J. Gen. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1006\/viro.2001.0965","article-title":"12-O-tetradecanoylphorbol-13-acetate induces Epstein-Barr virus reactivation via NF-kappaB and AP-1 as regulated by protein kinase C and mitogen-activated protein kinase","volume":"286","author":"Gao","year":"2001","journal-title":"Virology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1099\/vir.0.058040-0","article-title":"Microtubule depolymerization activates the Epstein-Barr virus lytic cycle through protein kinase C pathways in nasopharyngeal carcinoma cells","volume":"94","author":"Liu","year":"2013","journal-title":"J. Gen. Virol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1128\/JVI.01602-10","article-title":"Interplay between PKCdelta and Sp1 on histone deacetylase inhibitor-mediated Epstein-Barr virus reactivation","volume":"85","author":"Tsai","year":"2011","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6297","DOI":"10.1182\/blood-2011-01-332379","article-title":"Bortezomib induction of C\/EBPbeta mediates Epstein-Barr virus lytic activation in Burkitt lymphoma","volume":"117","author":"Shirley","year":"2011","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5528","DOI":"10.1182\/blood-2011-04-347112","article-title":"Endoplasmic reticulum stress causes EBV lytic replication","volume":"118","author":"Taylor","year":"2011","journal-title":"Blood"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lee, J., Kosowicz, J.G., Hayward, S.D., Desai, P., Stone, J., Lee, J.M., Liu, J.O., and Ambinder, R.F. (2019). Pharmacologic Activation of Lytic Epstein-Barr Virus Gene Expression without Virion Production. J. Virol., 93.","DOI":"10.1128\/JVI.00998-19"},{"key":"ref_27","first-page":"1920","article-title":"Chemotherapy induces lytic EBV replication and confers ganciclovir susceptibility to EBV-positive epithelial cell tumors","volume":"62","author":"Feng","year":"2002","journal-title":"Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1093\/jnci\/djh313","article-title":"Reactivation of latent Epstein-Barr virus by methotrexate: A potential contributor to methotrexate-associated lymphomas","volume":"96","author":"Feng","year":"2004","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6135","DOI":"10.1128\/JVI.75.13.6135-6142.2001","article-title":"Epstein-Barr virus immediate-early protein BRLF1 induces the lytic form of viral replication through a mechanism involving phosphatidylinositol-3 kinase activation","volume":"75","author":"Darr","year":"2001","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4901","DOI":"10.1158\/1078-0432.CCR-15-2242","article-title":"Lenalidomide, Thalidomide, and Pomalidomide Reactivate the Epstein-Barr Virus Lytic Cycle through Phosphoinositide 3-Kinase Signaling and Ikaros Expression","volume":"22","author":"Jones","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"31018","DOI":"10.18632\/oncotarget.5041","article-title":"Targeted therapy for Epstein-Barr virus-associated gastric carcinoma using low-dose gemcitabine-induced lytic activation","volume":"6","author":"Lee","year":"2015","journal-title":"Oncotarget"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Huang, S.Y., Fang, C.Y., Wu, C.C., Tsai, C.H., Lin, S.F., and Chen, J.Y. (2013). Reactive oxygen species mediate Epstein-Barr virus reactivation by N-methyl-N\u2019-nitro-N-nitrosoguanidine. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0084919"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Li, X., Burton, E.M., and Bhaduri-McIntosh, S. (2017). Chloroquine triggers Epstein-Barr virus replication through phosphorylation of KAP1\/TRIM28 in Burkitt lymphoma cells. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006249"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1128\/JVI.06334-11","article-title":"Dynamic chromatin environment of key lytic cycle regulatory regions of the Epstein-Barr virus genome","volume":"86","author":"Ramasubramanyan","year":"2012","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kraus, R.J., Yu, X., Cordes, B.A., Sathiamoorthi, S., Iempridee, T., Nawandar, D.M., Ma, S., Romero-Masters, J.C., McChesney, K.G., and Lin, Z. (2017). Hypoxia-inducible factor-1alpha plays roles in Epstein-Barr virus\u2019s natural life cycle and tumorigenesis by inducing lytic infection through direct binding to the immediate-early BZLF1 gene promoter. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006404"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Yiu, S.P.T., Hui, K.F., Choi, C.K., Kao, R.Y.T., Ma, C.W., Yang, D., and Chiang, A.K.S. (2018). Intracellular Iron Chelation by a Novel Compound, C7, Reactivates Epstein(-)Barr Virus (EBV) Lytic Cycle via the ERK-Autophagy Axis in EBV-Positive Epithelial Cancers. Cancers, 10.","DOI":"10.3390\/cancers10120505"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.bbamcr.2015.03.011","article-title":"PKC theta and p38 MAPK activate the EBV lytic cycle through autophagy induction","volume":"1853","author":"Gonnella","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/j.bbi.2010.04.013","article-title":"Glucocorticoids activate Epstein Barr virus lytic replication through the upregulation of immediate early BZLF1 gene expression","volume":"24","author":"Yang","year":"2010","journal-title":"Brain Behav. Immun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1182\/blood-2004-09-3748","article-title":"Azidothymidine inhibits NF-kappaB and induces Epstein-Barr virus gene expression in Burkitt lymphoma","volume":"106","author":"Kurokawa","year":"2005","journal-title":"Blood"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ejphar.2008.04.025","article-title":"Aspirin induces lytic cytotoxicity in Epstein-Barr virus-positive cells","volume":"589","author":"Liu","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ramayanti, O., Brinkkemper, M., Verkuijlen, S., Ritmaleni, L., Go, M.L., and Middeldorp, J.M. (2018). Curcuminoids as EBV Lytic Activators for Adjuvant Treatment in EBV-Positive Carcinomas. Cancers, 10.","DOI":"10.3390\/cancers10040089"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Choi, C.K., Ho, D.N., Hui, K.F., Kao, R.Y., and Chiang, A.K. (2015). Identification of Novel Small Organic Compounds with Diverse Structures for the Induction of Epstein-Barr Virus (EBV) Lytic Cycle in EBV-Positive Epithelial Malignancies. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0145994"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1021\/cb4006326","article-title":"Identification of a new class of small molecules that efficiently reactivate latent Epstein-Barr Virus","volume":"9","author":"Tikhmyanova","year":"2014","journal-title":"ACS Chem. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1007\/s00432-015-1969-3","article-title":"Epstein-Barr virus-targeted therapy in nasopharyngeal carcinoma","volume":"141","author":"Stoker","year":"2015","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1002\/ijc.27439","article-title":"Activation of lytic cycle of Epstein-Barr virus by suberoylanilide hydroxamic acid leads to apoptosis and tumor growth suppression of nasopharyngeal carcinoma","volume":"131","author":"Hui","year":"2012","journal-title":"Int. J. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Yiu, S.P.T., Hui, K.F., Munz, C., Lo, K.W., Tsao, S.W., Kao, R.Y.T., Yang, D., and Chiang, A.K.S. (2019). Autophagy-Dependent Reactivation of Epstein-Barr Virus Lytic Cycle and Combinatorial Effects of Autophagy-Dependent and Independent Lytic Inducers in Nasopharyngeal Carcinoma. Cancers, 11.","DOI":"10.3390\/cancers11121871"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1002\/ijc.24945","article-title":"Suberoylanilide hydroxamic acid induces viral lytic cycle in Epstein-Barr virus-positive epithelial malignancies and mediates enhanced cell death","volume":"126","author":"Hui","year":"2010","journal-title":"Int. J. Cancer"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"8762","DOI":"10.1158\/0008-5472.CAN-06-1006","article-title":"Valproic acid enhances the efficacy of chemotherapy in EBV-positive tumors by increasing lytic viral gene expression","volume":"66","author":"Feng","year":"2006","journal-title":"Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4706","DOI":"10.1128\/JVI.00116-08","article-title":"Histone hyperacetylation occurs on promoters of lytic cycle regulatory genes in Epstein-Barr virus-infected cell lines which are refractory to disruption of latency by histone deacetylase inhibitors","volume":"82","author":"Countryman","year":"2008","journal-title":"J. Virol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5612","DOI":"10.1128\/JVI.76.11.5612-5626.2002","article-title":"Protein kinase C-independent activation of the Epstein-Barr virus lytic cycle","volume":"76","author":"Gradoville","year":"2002","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/0042-6822(79)90455-0","article-title":"Induction of the Epstein-Barr virus (EBV) cycle in latently infected cells by n-butyrate","volume":"94","author":"Luka","year":"1979","journal-title":"Virology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1093\/annonc\/mdv596","article-title":"Epstein-Barr virus reactivation in extranodal natural killer\/T-cell lymphoma patients: A previously unrecognized serious adverse event in a pilot study with romidepsin","volume":"27","author":"Kim","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2259","DOI":"10.1016\/j.bmcl.2019.06.034","article-title":"Development of a novel inducer for EBV lytic therapy","volume":"29","author":"Tikhmyanova","year":"2019","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1128\/AAC.45.7.2082-2091.2001","article-title":"Induction of Epstein-Barr virus kinases to sensitize tumor cells to nucleoside analogues","volume":"45","author":"Moore","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5628","DOI":"10.1128\/JVI.02659-10","article-title":"Valproic acid antagonizes the capacity of other histone deacetylase inhibitors to activate the Epstein-barr virus lytic cycle","volume":"85","author":"Daigle","year":"2011","journal-title":"J. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1182\/blood-2004-05-1866","article-title":"Iron chelators with high antiproliferative activity up-regulate the expression of a growth inhibitory and metastasis suppressor gene: A link between iron metabolism and proliferation","volume":"104","author":"Le","year":"2004","journal-title":"Blood"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4811","DOI":"10.1128\/JVI.03706-13","article-title":"Epstein-Barr virus utilizes Ikaros in regulating its latent-lytic switch in B cells","volume":"88","author":"Iempridee","year":"2014","journal-title":"J. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Robinson, A.R., Kwek, S.S., and Kenney, S.C. (2012). The B-cell specific transcription factor, Oct-2, promotes Epstein-Barr virus latency by inhibiting the viral immediate-early protein, BZLF1. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002516"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Chun, Y., and Kim, J. (2018). Autophagy: An Essential Degradation Program for Cellular Homeostasis and Life. Cells, 7.","DOI":"10.3390\/cells7120278"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Das, G., Shravage, B.V., and Baehrecke, E.H. (2012). Regulation and function of autophagy during cell survival and cell death. Cold Spring Harb. Perspect. Biol., 4.","DOI":"10.1101\/cshperspect.a008813"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1111\/brv.12464","article-title":"The physiological roles of autophagy in the mammalian life cycle","volume":"94","author":"Wang","year":"2019","journal-title":"Biol. Rev. Camb. Philos. Soc."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1126\/science.1104904","article-title":"Endogenous MHC class II processing of a viral nuclear antigen after autophagy","volume":"307","author":"Paludan","year":"2005","journal-title":"Science"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/s41419-018-0668-9","article-title":"Transcriptional and epigenetic modulation of autophagy promotes EBV oncoprotein EBNA3C induced B-cell survival","volume":"9","author":"Bhattacharjee","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"6940","DOI":"10.1128\/JVI.03371-14","article-title":"Epstein-Barr virus latent membrane protein 2 induces autophagy to promote abnormal acinus formation","volume":"89","author":"Fotheringham","year":"2015","journal-title":"J. Virol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2833","DOI":"10.1038\/sj.onc.1210946","article-title":"The latent membrane protein 1 oncogene modifies B-cell physiology by regulating autophagy","volume":"27","author":"Lee","year":"2008","journal-title":"Oncogene"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1080\/15548627.2015.1115939","article-title":"Constitutive autophagy contributes to resistance to TP53-mediated apoptosis in Epstein-Barr virus-positive latency III B-cell lymphoproliferations","volume":"11","author":"Pujals","year":"2015","journal-title":"Autophagy"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"12133","DOI":"10.1128\/JVI.02033-14","article-title":"Regulation of autophagic activation by Rta of Epstein-Barr virus via the extracellular signal-regulated kinase pathway","volume":"88","author":"Hung","year":"2014","journal-title":"J. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e1876","DOI":"10.1038\/cddis.2015.156","article-title":"Inhibition of autophagy in EBV-positive Burkitt\u2019s lymphoma cells enhances EBV lytic genes expression and replication","volume":"6","author":"Colavita","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.virusres.2017.11.021","article-title":"Rapamycin enhances lytic replication of Epstein-Barr virus in gastric carcinoma cells by increasing the transcriptional activities of immediate-early lytic promoters","volume":"244","author":"Wang","year":"2018","journal-title":"Virus Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/1743-422X-11-110","article-title":"Inhibition of mTORC1 inhibits lytic replication of Epstein-Barr virus in a cell-type specific manner","volume":"11","author":"Adamson","year":"2014","journal-title":"Virol. J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"431S","DOI":"10.3945\/ajcn.113.071290","article-title":"Genistein inhibits human prostate cancer cell detachment, invasion, and metastasis","volume":"100","author":"Pavese","year":"2014","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s11010-014-1974-x","article-title":"Genistein induces apoptosis and autophagy in human breast MCF-7 cells by modulating the expression of proapoptotic factors and oxidative stress enzymes","volume":"390","author":"Prietsch","year":"2014","journal-title":"Mol. Cell Biochem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e1509","DOI":"10.1038\/cddis.2014.467","article-title":"Regulation of autophagy by polyphenolic compounds as a potential therapeutic strategy for cancer","volume":"5","author":"Hasima","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4656","DOI":"10.1021\/acs.jmedchem.7b01019","article-title":"Design of Small Molecule Autophagy Modulators: A Promising Druggable Strategy","volume":"61","author":"He","year":"2018","journal-title":"J. Med. Chem"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1101\/gad.183434.111","article-title":"NF-kappaB, the first quarter-century: Remarkable progress and outstanding questions","volume":"26","author":"Hayden","year":"2012","journal-title":"Genes Dev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.coi.2008.04.010","article-title":"Activation-dependent induction of Blimp-1","volume":"20","author":"Calame","year":"2008","journal-title":"Curr. Opin. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1161\/01.ATV.0000258979.92828.bc","article-title":"Reactive oxygen species activate the HIF-1alpha promoter via a functional NFkappaB site","volume":"27","author":"Bonello","year":"2007","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4374","DOI":"10.1128\/MCB.02020-06","article-title":"NF-kappaB regulation of YY1 inhibits skeletal myogenesis through transcriptional silencing of myofibrillar genes","volume":"27","author":"Wang","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1073\/pnas.2237183100","article-title":"Epstein-Barr virus latent infection membrane protein 1 TRAF-binding site induces NIK\/IKK alpha-dependent noncanonical NF-kappaB activation","volume":"101","author":"Luftig","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"51134","DOI":"10.1074\/jbc.M304771200","article-title":"Latent membrane protein 1 of Epstein-Barr virus stimulates processing of NF-kappa B2 p100 to p52","volume":"278","author":"Atkinson","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Verhoeven, R.J.A., Tong, S., Zong, J., Chen, Y., Tsao, S.W., Pan, J., and Chen, H. (2018). NF-kappaB Signaling Regulates Epstein-Barr Virus BamHI-Q-Driven EBNA1 Expression. Cancers, 10.","DOI":"10.3390\/cancers10040119"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1476-4598-9-1","article-title":"Epstein-Barr virus-encoded EBNA1 inhibits the canonical NF-kappaB pathway in carcinoma cells by inhibiting IKK phosphorylation","volume":"9","author":"Valentine","year":"2010","journal-title":"Mol. Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1128\/JVI.78.1.544-549.2004","article-title":"Epstein-Barr virus immediate-early protein BZLF1 inhibits tumor necrosis factor alpha-induced signaling and apoptosis by downregulating tumor necrosis factor receptor 1","volume":"78","author":"Morrison","year":"2004","journal-title":"J. Virol."},{"key":"ref_84","first-page":"1939","article-title":"The bZIP transactivator of Epstein-Barr virus, BZLF1, functionally and physically interacts with the p65 subunit of NF-kappa B","volume":"14","author":"Gutsch","year":"1994","journal-title":"Mol. Cell Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1126\/science.2173142","article-title":"Expression of interleukin-10 activity by Epstein-Barr virus protein BCRF1","volume":"250","author":"Hsu","year":"1990","journal-title":"Science"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3878","DOI":"10.1128\/jvi.63.9.3878-3883.1989","article-title":"The Epstein-Barr virus BMLF1 promoter contains an enhancer element that is responsive to the BZLF1 and BRLF1 transactivators","volume":"63","author":"Kenney","year":"1989","journal-title":"J. Virol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"10563","DOI":"10.1096\/fj.201901196RR","article-title":"Epstein-Barr virus tegument protein BGLF2 inhibits NF-kappaB activity by preventing p65 Ser536 phosphorylation","volume":"33","author":"Chen","year":"2019","journal-title":"FASEB J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"8532","DOI":"10.1128\/JVI.77.15.8532-8540.2003","article-title":"NF-kappaB inhibits gammaherpesvirus lytic replication","volume":"77","author":"Brown","year":"2003","journal-title":"J. Virol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"10029","DOI":"10.1128\/JVI.02241-06","article-title":"Bortezomib induces apoptosis of Epstein-Barr virus (EBV)-transformed B cells and prolongs survival of mice inoculated with EBV-transformed B cells","volume":"81","author":"Zou","year":"2007","journal-title":"J. Virol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"12064","DOI":"10.1038\/s41598-019-48590-7","article-title":"The anti-tumor function of the IKK inhibitor PS1145 and high levels of p65 and KLF4 are associated with the drug resistance in nasopharyngeal carcinoma cells","volume":"9","author":"Lung","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"6475","DOI":"10.1128\/JVI.00613-16","article-title":"NF-kappaB Signaling Regulates Expression of Epstein-Barr Virus BART MicroRNAs and Long Noncoding RNAs in Nasopharyngeal Carcinoma","volume":"90","author":"Verhoeven","year":"2016","journal-title":"J. Virol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"477","DOI":"10.3892\/mmr.2012.959","article-title":"Parthenolide induces apoptosis and lytic cytotoxicity in Epstein-Barr virus-positive Burkitt lymphoma","volume":"6","author":"Li","year":"2012","journal-title":"Mol. Med. Rep."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1126\/science.277.5332.1630","article-title":"STATs and gene regulation","volume":"277","author":"Darnell","year":"1997","journal-title":"Science"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"24391","DOI":"10.1016\/S0021-9258(19)51096-1","article-title":"Acute phase response factor and additional members of the interferon-stimulated gene factor 3 family integrate diverse signals from cytokines, interferons, and growth factors","volume":"269","author":"Raz","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2766","DOI":"10.1158\/0008-5472.CAN-08-3070","article-title":"Activation of DNA methyltransferase 1 by EBV latent membrane protein 2A leads to promoter hypermethylation of PTEN gene in gastric carcinoma","volume":"69","author":"Hino","year":"2009","journal-title":"Cancer Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"4139","DOI":"10.1128\/JVI.77.7.4139-4148.2003","article-title":"A positive autoregulatory loop of LMP1 expression and STAT activation in epithelial cells latently infected with Epstein-Barr virus","volume":"77","author":"Chen","year":"2003","journal-title":"J. Virol."},{"key":"ref_97","first-page":"185","article-title":"Role of Epstein-Barr virus encoded latent membrane protein 1 in the carcinogenesis of nasopharyngeal carcinoma","volume":"4","author":"Zheng","year":"2007","journal-title":"Cell Mol. Immunol"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Shair, K.H., Bendt, K.M., Edwards, R.H., Bedford, E.C., Nielsen, J.N., and Raab-Traub, N. (2007). EBV latent membrane protein 1 activates Akt, NFkappaB, and Stat3 in B cell lymphomas. PLoS Pathog., 3.","DOI":"10.1371\/journal.ppat.0030166"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"31077","DOI":"10.18632\/oncotarget.25780","article-title":"STAT3 is constitutively activated in chronic active Epstein-Barr virus infection and can be a therapeutic target","volume":"9","author":"Onozawa","year":"2018","journal-title":"Oncotarget"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1128\/JVI.01745-09","article-title":"Upregulation of STAT3 marks Burkitt lymphoma cells refractory to Epstein-Barr virus lytic cycle induction by HDAC inhibitors","volume":"84","author":"Daigle","year":"2010","journal-title":"J. Virol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"11438","DOI":"10.1128\/JVI.01762-13","article-title":"Signal transducer and activator of transcription 3 limits Epstein-Barr virus lytic activation in B lymphocytes","volume":"87","author":"Hill","year":"2013","journal-title":"J. Virol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s13046-015-0133-x","article-title":"Icaritin induces lytic cytotoxicity in extranodal NK\/T-cell lymphoma","volume":"34","author":"Wu","year":"2015","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.3892\/or.2017.5489","article-title":"Berberine inhibits the proliferation of human nasopharyngeal carcinoma cells via an Epstein-Barr virus nuclear antigen 1-dependent mechanism","volume":"37","author":"Wang","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1093\/carcin\/bgp253","article-title":"Cucurbitacin I elicits anoikis sensitization, inhibits cellular invasion and in vivo tumor formation ability of nasopharyngeal carcinoma cells","volume":"30","author":"Lui","year":"2009","journal-title":"Carcinogenesis"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.ccr.2009.10.015","article-title":"The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors","volume":"16","author":"Hedvat","year":"2009","journal-title":"Cancer Cell"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1038\/nm1010-1085","article-title":"Peering into the aftermath: JAKi rips STAT3 in cancer","volume":"16","author":"Greten","year":"2010","journal-title":"Nat. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"7391","DOI":"10.1073\/pnas.0609757104","article-title":"Selective chemical probe inhibitor of Stat3, identified through structure-based virtual screening, induces antitumor activity","volume":"104","author":"Siddiquee","year":"2007","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"4700","DOI":"10.1073\/pnas.0409894102","article-title":"A low-molecular-weight compound discovered through virtual database screening inhibits Stat3 function in breast cancer cells","volume":"102","author":"Song","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.bbrc.2009.01.137","article-title":"Novel high-throughput screening system for identifying STAT3-SH2 antagonists","volume":"380","author":"Uehara","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1158\/0008-5472.CAN-12-3175","article-title":"A novel inhibitor of STAT3 homodimerization selectively suppresses STAT3 activity and malignant transformation","volume":"73","author":"Zhang","year":"2013","journal-title":"Cancer Res."},{"key":"ref_111","first-page":"495","article-title":"Telomerase activation by Epstein-Barr virus latent membrane protein 1 is associated with c-Myc expression in human nasopharyngeal epithelial cells","volume":"23","author":"Yang","year":"2004","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"10175","DOI":"10.1128\/JVI.00321-08","article-title":"Latent membrane protein 1 of Epstein-Barr virus activates the hTERT promoter and enhances telomerase activity in B lymphocytes","volume":"82","author":"Terrin","year":"2008","journal-title":"J. Virol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e1774","DOI":"10.1038\/cddis.2015.145","article-title":"Cross talk between EBV and telomerase: The role of TERT and NOTCH2 in the switch of latent\/lytic cycle of the virus","volume":"6","author":"Giunco","year":"2015","journal-title":"Cell Death Dis."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1158\/1078-0432.CCR-12-2537","article-title":"hTERT inhibition triggers Epstein-Barr virus lytic cycle and apoptosis in immortalized and transformed B cells: A basis for new therapies","volume":"19","author":"Giunco","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1016\/j.str.2015.08.006","article-title":"Structural Basis of Telomerase Inhibition by the Highly Specific BIBR1532","volume":"23","author":"Bryan","year":"2015","journal-title":"Structure"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"15566","DOI":"10.1074\/jbc.M201266200","article-title":"Mechanism of human telomerase inhibition by BIBR1532, a synthetic, non-nucleosidic drug candidate","volume":"277","author":"Pascolo","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"6958","DOI":"10.1093\/emboj\/20.24.6958","article-title":"A highly selective telomerase inhibitor limiting human cancer cell proliferation","volume":"20","author":"Damm","year":"2001","journal-title":"EMBO J."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1182\/blood-2003-12-4322","article-title":"Selective cytotoxicity and telomere damage in leukemia cells using the telomerase inhibitor BIBR1532","volume":"105","author":"Kull","year":"2005","journal-title":"Blood"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e2562","DOI":"10.1038\/cddis.2016.425","article-title":"Short-term inhibition of TERT induces telomere length-independent cell cycle arrest and apoptotic response in EBV-immortalized and transformed B cells","volume":"7","author":"Celeghin","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_120","first-page":"657","article-title":"Telomere shortening and growth inhibition of human cancer cells by novel synthetic telomerase inhibitors MST-312, MST-295, and MST-1991","volume":"1","author":"Seimiya","year":"2002","journal-title":"Mol. Cancer Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/1476-4598-10-96","article-title":"Inhibition of telomerase activity preferentially targets aldehyde dehydrogenase-positive cancer stem-like cells in lung cancer","volume":"10","author":"Serrano","year":"2011","journal-title":"Mol. Cancer"},{"key":"ref_122","first-page":"283","article-title":"MST-312 Alters Telomere Dynamics, Gene Expression Profiles and Growth in Human Breast Cancer Cells","volume":"7","author":"Gurung","year":"2014","journal-title":"J. Nutrigenet. Nutrigenomics"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1097\/CAD.0000000000000508","article-title":"Long-term exposure to MST-312 leads to telomerase reverse transcriptase overexpression in MCF-7 breast cancer cells","volume":"28","author":"Morais","year":"2017","journal-title":"Anticancer Drugs"},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Ichikawa, T., Okuno, Y., Sato, Y., Goshima, F., Yoshiyama, H., Kanda, T., Kimura, H., and Murata, T. (2018). Regulation of Epstein-Barr Virus Life Cycle and Cell Proliferation by Histone H3K27 Methyltransferase EZH2 in Akata Cells. mSphere, 3.","DOI":"10.1128\/mSphere.00478-18"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"e2213","DOI":"10.1038\/cddis.2016.117","article-title":"Nrf2-driven TERT regulates pentose phosphate pathway in glioblastoma","volume":"7","author":"Ahmad","year":"2016","journal-title":"Cell Death Dis."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1111\/jnc.14152","article-title":"Telomerase reverse transcriptase (TERT)-enhancer of zeste homolog 2 (EZH2) network regulates lipid metabolism and DNA damage responses in glioblastoma","volume":"143","author":"Ahmad","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.cell.2009.03.045","article-title":"The canonical Notch signaling pathway: Unfolding the activation mechanism","volume":"137","author":"Kopan","year":"2009","journal-title":"Cell"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"5506","DOI":"10.1182\/blood-2008-11-190090","article-title":"Notch1, Notch2, and Epstein-Barr virus-encoded nuclear antigen 2 signaling differentially affects proliferation and survival of Epstein-Barr virus-infected B cells","volume":"113","author":"Kohlhof","year":"2009","journal-title":"Blood"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.virol.2007.10.009","article-title":"An auto-regulatory loop for EBV LMP2A involves activation of Notch","volume":"371","author":"Anderson","year":"2008","journal-title":"Virology"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"12065","DOI":"10.1128\/JVI.01431-14","article-title":"Counteracting effects of cellular Notch and Epstein-Barr virus EBNA2: Implications for stromal effects on virus-host interactions","volume":"88","author":"Rowe","year":"2014","journal-title":"J. Virol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1158\/0008-5472.CAN-11-3067","article-title":"Kaposi sarcoma herpesvirus promotes endothelial-to-mesenchymal transition through Notch-dependent signaling","volume":"72","author":"Gasperini","year":"2012","journal-title":"Cancer Res."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Li, S., Hu, H., He, Z., Liang, D., Sun, R., and Lan, K. (2016). Fine-Tuning of the Kaposi\u2019s Sarcoma-Associated Herpesvirus Life Cycle in Neighboring Cells through the RTA-JAG1-Notch Pathway. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005900"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1111\/j.1601-0825.2006.01334.x","article-title":"Gamma-secretase inhibitors exerts antitumor activity via down-regulation of Notch and Nuclear factor kappa B in human tongue carcinoma cells","volume":"13","author":"Yao","year":"2007","journal-title":"Oral Dis."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.semcancer.2006.07.014","article-title":"The c-Myc target gene network","volume":"16","author":"Dang","year":"2006","journal-title":"Semin. Cancer Biol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/nrm1703","article-title":"Transcriptional regulation and transformation by Myc proteins","volume":"6","author":"Adhikary","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Guo, R., Jiang, C., Zhang, Y., Govande, A., Trudeau, S.J., Chen, F., Fry, C.J., Puri, R., Wolinsky, E., and Schineller, M. (2020). MYC Controls the Epstein-Barr Virus Lytic Switch. Mol. Cell.","DOI":"10.1016\/j.molcel.2020.03.025"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41392-018-0008-7","article-title":"Targeting oncogenic Myc as a strategy for cancer treatment","volume":"3","author":"Chen","year":"2018","journal-title":"Signal. Transduct. Target. Ther."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.cell.2011.08.017","article-title":"BET bromodomain inhibition as a therapeutic strategy to target c-Myc","volume":"146","author":"Delmore","year":"2011","journal-title":"Cell"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1038\/nature09504","article-title":"Selective inhibition of BET bromodomains","volume":"468","author":"Filippakopoulos","year":"2010","journal-title":"Nature"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1038\/nm.4180","article-title":"HAUSP deubiquitinates and stabilizes N-Myc in neuroblastoma","volume":"22","author":"Tavana","year":"2016","journal-title":"Nat. Med."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.ccr.2008.12.005","article-title":"Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma","volume":"15","author":"Otto","year":"2009","journal-title":"Cancer Cell"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"3830","DOI":"10.1073\/pnas.062036999","article-title":"Small-molecule antagonists of Myc\/Max dimerization inhibit Myc-induced transformation of chicken embryo fibroblasts","volume":"99","author":"Berg","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"13284","DOI":"10.1074\/jbc.M116.751644","article-title":"Bromodomain and extraterminal inhibitors block the Epstein-Barr virus lytic cycle at two distinct steps","volume":"292","author":"Keck","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/nature13393","article-title":"Targeting transcription regulation in cancer with a covalent CDK7 inhibitor","volume":"511","author":"Kwiatkowski","year":"2014","journal-title":"Nature"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1128\/AAC.04534-14","article-title":"A novel CDK7 inhibitor of the Pyrazolotriazine class exerts broad-spectrum antiviral activity at nanomolar concentrations","volume":"59","author":"Hutterer","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"6614","DOI":"10.1158\/0008-5472.CAN-17-1143","article-title":"Super-Enhancers Promote Transcriptional Dysregulation in Nasopharyngeal Carcinoma","volume":"77","author":"Yuan","year":"2017","journal-title":"Cancer Res."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1038\/sj.onc.1209205","article-title":"EBV EBNA 2 stimulates CDK9-dependent transcription and RNA polymerase II phosphorylation on serine 5","volume":"25","author":"Webb","year":"2006","journal-title":"Oncogene"},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Sato, Y., Watanabe, T., Suzuki, C., Abe, Y., Masud, H., Inagaki, T., Yoshida, M., Suzuki, T., Goshima, F., and Adachi, J. (2019). S-Like-Phase Cyclin-Dependent Kinases Stabilize the Epstein-Barr Virus BDLF4 Protein to Temporally Control Late Gene Transcription. J. Virol., 93.","DOI":"10.1128\/JVI.01707-18"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.juro.2013.07.019","article-title":"Intravesical instillation of c-MYC inhibitor KSI-3716 suppresses orthotopic bladder tumor growth","volume":"191","author":"Jeong","year":"2014","journal-title":"J. Urol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.ccell.2019.10.001","article-title":"Small-Molecule MYC Inhibitors Suppress Tumor Growth and Enhance Immunotherapy","volume":"36","author":"Han","year":"2019","journal-title":"Cancer Cell"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1021\/acschembio.7b00799","article-title":"Targeted Disruption of Myc-Max Oncoprotein Complex by a Small Molecule","volume":"12","author":"Choi","year":"2017","journal-title":"ACS Chem. Biol."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Muller, I., Larsson, K., Frenzel, A., Oliynyk, G., Zirath, H., Prochownik, E.V., Westwood, N.J., and Henriksson, M.A. (2014). Targeting of the MYCN protein with small molecule c-MYC inhibitors. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097285"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"10064","DOI":"10.1038\/s41598-018-28107-4","article-title":"A selective high affinity MYC-binding compound inhibits MYC:MAX interaction and MYC-dependent tumor cell proliferation","volume":"8","author":"Castell","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"22298","DOI":"10.1038\/srep22298","article-title":"Structure-based Inhibitor Design for the Intrinsically Disordered Protein c-Myc","volume":"6","author":"Yu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Yao, R., Sun, X., Xie, Y., Sun, X., Yao, Y., Li, H., Li, Z., Gao, J., and Xu, K. (2018). Identification of a novel c-Myc inhibitor with antitumor effects on multiple myeloma cells. Biosci. Rep., 38.","DOI":"10.1042\/BSR20181027"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.ejmech.2018.09.023","article-title":"Computer-aided drug discovery of Myc-Max inhibitors as potential therapeutics for prostate cancer","volume":"160","author":"Carabet","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"3002","DOI":"10.1021\/jm501440q","article-title":"Perturbation of the c-Myc-Max protein-protein interaction via synthetic alpha-helix mimetics","volume":"58","author":"Jung","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/978-1-60761-244-5_3","article-title":"X-ray crystallography in drug discovery","volume":"572","author":"Carvalho","year":"2009","journal-title":"Methods Mol. Biol."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Sugiki, T., Furuita, K., Fujiwara, T., and Kojima, C. (2018). Current NMR Techniques for Structure-Based Drug Discovery. Molecules, 23.","DOI":"10.3390\/molecules23010148"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/nrd.2018.77","article-title":"Cryo-EM in drug discovery: Achievements, limitations and prospects","volume":"17","author":"Renaud","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Jiang, L., Lung, H.L., Huang, T., Lan, R., Zha, S., Chan, L.S., Thor, W., Tsoi, T.H., Chau, H.F., and Borestrom, C. (2019). Reactivation of Epstein-Barr virus by a dual-responsive fluorescent EBNA1-targeting agent with Zn(2+)-chelating function. Proc. Natl. Acad. Sci. USA.","DOI":"10.1073\/pnas.1915372116"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"5307","DOI":"10.7150\/thno.26823","article-title":"EBNA1-targeted inhibitors: Novel approaches for the treatment of Epstein-Barr virus-associated cancers","volume":"8","author":"Jiang","year":"2018","journal-title":"Theranostics"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"15632","DOI":"10.1039\/C8NR05015E","article-title":"Responsive upconversion nanoprobe for monitoring and inhibition of EBV-associated cancers via targeting EBNA1","volume":"10","author":"Zha","year":"2018","journal-title":"Nanoscale"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"6517","DOI":"10.1039\/C4CC01589D","article-title":"EBNA1-specific luminescent small molecules for the imaging and inhibition of latent EBV-infected tumor cells","volume":"50","author":"Jiang","year":"2014","journal-title":"Chem. Commun."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/1357-2725(96)00050-7","article-title":"The Oct-2 transcription factor","volume":"28","author":"Latchman","year":"1996","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/B978-0-12-385991-4.00005-2","article-title":"Pax5: A master regulator of B cell development and leukemogenesis","volume":"111","author":"Medvedovic","year":"2011","journal-title":"Adv. Immunol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"8053","DOI":"10.1128\/JVI.00546-13","article-title":"The B-cell-specific transcription factor and master regulator Pax5 promotes Epstein-Barr virus latency by negatively regulating the viral immediate early protein BZLF1","volume":"87","author":"Raver","year":"2013","journal-title":"J. Virol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1158\/1078-0432.CCR-07-0828","article-title":"Nuclear factor-Y and Epstein Barr virus in nasopharyngeal cancer","volume":"14","author":"Chia","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.chom.2017.04.005","article-title":"CRISPR\/Cas9 Screens Reveal Epstein-Barr Virus-Transformed B Cell Host Dependency Factors","volume":"21","author":"Ma","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_170","first-page":"3078","article-title":"Therapeutic Targeting of Interferon Regulatory Factor 4 with Next Generation Antisense Oligonucleotides Produces Robust in Vivo Antitumor Activity in Preclinical Models of Multiple Myeloma","volume":"130","author":"Zhou","year":"2017","journal-title":"Blood"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"5545","DOI":"10.1182\/blood-2019-130910","article-title":"A High-Throughput Drug Screen Reveals a Novel Compound Class That Significantly Depletes IRF4 Expression in Multiple Myeloma","volume":"134","author":"Lightbody","year":"2019","journal-title":"Blood"},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"Chang, Y.H., Lee, C.P., Su, M.T., Wang, J.T., Chen, J.Y., Lin, S.F., Tsai, C.H., Hsieh, M.J., Takada, K., and Chen, M.R. (2012). Epstein-Barr virus BGLF4 kinase retards cellular S-phase progression and induces chromosomal abnormality. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039217"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"8583","DOI":"10.18632\/oncotarget.2323","article-title":"Epstein-Barr virus BALF3 mediates genomic instability and progressive malignancy in nasopharyngeal carcinoma","volume":"5","author":"Chiu","year":"2014","journal-title":"Oncotarget"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1093\/nar\/gkp1169","article-title":"Epstein-Barr virus DNase (BGLF5) induces genomic instability in human epithelial cells","volume":"38","author":"Wu","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"14257","DOI":"10.1038\/ncomms14257","article-title":"Epstein-Barr virus particles induce centrosome amplification and chromosomal instability","volume":"8","author":"Shumilov","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"8097","DOI":"10.1128\/JVI.00588-12","article-title":"Epstein-Barr virus BPLF1 deubiquitinates PCNA and attenuates polymerase eta recruitment to DNA damage sites","volume":"86","author":"Whitehurst","year":"2012","journal-title":"J. Virol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/8\/2142\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:53:47Z","timestamp":1760176427000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/12\/8\/2142"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,2]]},"references-count":176,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["cancers12082142"],"URL":"https:\/\/doi.org\/10.3390\/cancers12082142","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,2]]}}}