{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T08:16:21Z","timestamp":1788682581161,"version":"build-2803163510"},"reference-count":113,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Nasopharyngeal carcinoma (NPC) is a rare malignancy with a distinct epidemiological pattern and is most often associated with Epstein\u2013Barr virus (EBV). EBV plays a critical role in NPC pathogenesis, with viral proteins driving oncogenesis by altering immune regulation, apoptosis, and tumor progression. The unique molecular landscape of NPC presents both challenges and opportunities for therapeutic development, particularly in the recurrent and metastatic (R\/M) setting, where treatment resistance remains a major hurdle. While platinum-based chemotherapy has traditionally been the standard of care for R\/M NPC, immune checkpoint inhibitors (ICIs) have emerged as a key component of treatment. However, both intrinsic and acquired resistance to PD-1\/PD-L1 blockade underscore the need for alternative strategies, including modulation of alternative immune checkpoints and simultaneous engagement of non-redundant pathways to enhance responses and durability. Leveraging EBV-driven biology, emerging immunotherapeutic approaches, such as EBV-specific adoptive cellular therapies and therapeutic vaccines, aim to induce durable immunity to viral proteins. Additionally, targeted therapies including receptor tyrosine kinase inhibitors, epigenetic modulators, and antibody\u2013drug conjugates are redefining precision medicine by selectively delivering cytotoxic agents to tumors. With growing insights into the biology of NPC and evolving therapeutics, the integration of immunotherapy, targeted agents, and biomarker-driven strategies is poised to transform NPC treatment, emphasizing biology-driven, multimodal approaches to optimize patient outcomes.<\/jats:p>","DOI":"10.3390\/curroncol32090479","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T10:35:17Z","timestamp":1756204517000},"page":"479","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Novel Therapeutic Development for Nasopharyngeal Carcinoma"],"prefix":"10.3390","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3181-1758","authenticated-orcid":false,"given":"Jongwoo","family":"Kim","sequence":"first","affiliation":[{"name":"MetroWest Medical Center, Framingham, MA 01702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunjoo","family":"Lee","sequence":"additional","affiliation":[{"name":"Medicine-Hematology and Medical Oncology, Massachusetts General Hospital, Boston, MA 02114, USA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Ragon Institute, Cambridge, MA 02139, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seoin","family":"Kim","sequence":"additional","affiliation":[{"name":"MetroWest Medical Center, Framingham, MA 01702, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1052-0734","authenticated-orcid":false,"given":"Jong Chul","family":"Park","sequence":"additional","affiliation":[{"name":"Medicine-Hematology and Medical Oncology, Massachusetts General Hospital, Boston, MA 02114, USA"},{"name":"Department of Medicine, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e49968","DOI":"10.2196\/49968","article-title":"Nasopharyngeal Cancer Incidence and Mortality in 185 Countries in 2020 and the Projected Burden in 2040: Population-Based Global Epidemiological Profiling","volume":"9","author":"Zhang","year":"2023","journal-title":"JMIR Public Health Surveill."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"769","DOI":"10.2147\/CLEP.S490023","article-title":"Gender-Specific Survival of Nasopharyngeal Carcinoma in Endemic and Non-Endemic Areas Based on the US SEER Database and a Chinese Single-Institutional Registry","volume":"16","author":"Guo","year":"2024","journal-title":"Clin. Epidemiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"85","DOI":"10.14639\/0392-100X-N2222","article-title":"Nasopharyngeal carcinoma. A \u201cdifferent\u201d head and neck tumour. Part A: From histology to staging","volume":"43","year":"2023","journal-title":"Acta Otorhinolaryngol. Ital."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/j.humimm.2009.08.005","article-title":"Association of human leukocyte antigens with nasopharyngeal carcinoma in high-risk multiplex families in Taiwan","volume":"70","author":"Yu","year":"2009","journal-title":"Hum. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Su, Z.Y., Siak, P.Y., Leong, C.-O., and Cheah, S.-C. (2023). The role of Epstein-Barr virus in nasopharyngeal carcinoma. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1116143"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e131","DOI":"10.1038\/emm.2014.84","article-title":"Epstein-Barr virus latent genes","volume":"47","author":"Kang","year":"2015","journal-title":"Exp. Mol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ahmed, N., Abusalah, M., Farzand, A., Absar, M., Yusof, N.Y., Rabaan, A.A., AlSaihati, H., Alshengeti, A., Alwarthan, S., and Alsuwailem, H.S. (2022). Updates on Epstein-Barr Virus (EBV)-Associated Nasopharyngeal Carcinoma: Emphasis on the Latent Gene Products of EBV. Medicina, 59.","DOI":"10.3390\/medicina59010002"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"154","DOI":"10.5501\/wjv.v1.i6.154","article-title":"Roles of the PI3K\/Akt pathway in Epstein-Barr virus-induced cancers and therapeutic implications","volume":"1","author":"Chen","year":"2012","journal-title":"World J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"149","DOI":"10.14694\/EdBook_AM.2014.34.149","article-title":"Epstein-Barr virus as a paradigm in nasopharyngeal cancer: From lab to clinic","volume":"34","author":"Raghupathy","year":"2014","journal-title":"Am. Soc. Clin. Oncol. Educ. Book"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1073\/pnas.0810619106","article-title":"The Epstein-Barr virus nuclear antigen-1 promotes genomic instability via induction of reactive oxygen species","volume":"106","author":"Gruhne","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Hau, P.M., Lung, H.L., Wu, M., Tsang, C.M., Wong, K.L., Mak, N.K., and Lo, K.W. (2020). Targeting Epstein-Barr Virus in Nasopharyngeal Carcinoma. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.00600"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1084\/jem.20072581","article-title":"An Epstein-Barr virus-encoded microRNA targets PUMA to promote host cell survival","volume":"205","author":"Choy","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"565","DOI":"10.7150\/ijbs.24562","article-title":"Epstein-Barr virus-encoded microRNAs as regulators in host immune responses","volume":"14","author":"Wang","year":"2018","journal-title":"Int. J. Biol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.ajhg.2009.07.007","article-title":"Genome-wide association study reveals multiple nasopharyngeal carcinoma-associated loci within the HLA region at chromosome 6p21.3","volume":"85","author":"Tse","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6308","DOI":"10.1002\/cam4.1838","article-title":"Fine-mapping of HLA class I and class II genes identified two independent novel variants associated with nasopharyngeal carcinoma susceptibility","volume":"7","author":"Wang","year":"2018","journal-title":"Cancer Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/1756-9966-28-160","article-title":"Methylation associated inactivation of RASSF1A and its synergistic effect with activated K-Ras in nasopharyngeal carcinoma","volume":"28","author":"Wang","year":"2009","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1177\/17246008211065472","article-title":"Hypermethylation of the RASSF1A gene promoter as the tumor DNA marker for nasopharyngeal carcinoma","volume":"37","author":"Lao","year":"2022","journal-title":"Int. J. Biol. Markers"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Leong, M.M.L., and Lung, M.L. (2021). The Impact of Epstein-Barr Virus Infection on Epigenetic Regulation of Host Cell Gene Expression in Epithelial and Lymphocytic Malignancies. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.629780"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.7150\/thno.82690","article-title":"Nasopharyngeal carcinoma ecology theory: Cancer as multidimensional spatiotemporal \u201cunity of ecology and evolution\u201d pathological ecosystem","volume":"13","author":"Luo","year":"2023","journal-title":"Theranostics"},{"key":"ref_20","first-page":"463","article-title":"Rethinking cancer","volume":"47","author":"Luo","year":"2025","journal-title":"Zhonghua Zhong Liu Za Zhi"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1001\/jamaoncol.2024.4354","article-title":"Ninth Version of the AJCC and UICC Nasopharyngeal Cancer TNM Staging Classification","volume":"10","author":"Pan","year":"2024","journal-title":"JAMA Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"102245","DOI":"10.1016\/j.tranon.2024.102245","article-title":"MRI-based deep learning and radiomics for predicting the efficacy of PD-1 inhibitor combined with induction chemotherapy in advanced nasopharyngeal carcinoma: A prospective cohort study","volume":"52","author":"Wang","year":"2025","journal-title":"Transl. Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Gu, B., Meng, M., Bi, L., Kim, J., Feng, D.D., and Song, S. (2022). Prediction of 5-year progression-free survival in advanced nasopharyngeal carcinoma with pretreatment PET\/CT using multi-modality deep learning-based radiomics. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.899351"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"565","DOI":"10.5732\/cjc.010.10547","article-title":"Treatment outcomes for different subgroups of nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy","volume":"30","author":"Su","year":"2011","journal-title":"Chin. J. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s00432-023-05547-8","article-title":"Nasopharyngeal carcinoma: Nationwide trends in subtype-specific incidence and survival over 3 decades in a non-endemic area","volume":"150","author":"Plaat","year":"2024","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Chen, H., Huang, Z., Chen, L., Li, Y., Zhao, T., and Wei, Q. (2021). Characteristics of Early Death in Patients with Localized Nasopharyngeal Cancer: A Population-Based SEER Analysis. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.580220"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6","DOI":"10.11604\/pamj.2022.41.6.28946","article-title":"Prognostic value of Epstein-Barr virus DNA load in nasopharyngeal carcinoma: A meta-analysis","volume":"41","author":"Alami","year":"2022","journal-title":"Pan Afr. Med. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2","DOI":"10.6004\/jnccn.2025.0007","article-title":"NCCN Guidelines\u00ae Insights: Head and Neck Cancers, Version 2.2025","volume":"23","author":"Colevas","year":"2025","journal-title":"J. Natl. Compr. Canc Netw."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/S1470-2045(20)30673-2","article-title":"Endoscopic surgery compared with intensity-modulated radiotherapy in resectable locally recurrent nasopharyngeal carcinoma: A multicentre, open-label, randomised, controlled, phase 3 trial","volume":"22","author":"Liu","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/S0140-6736(23)00269-6","article-title":"Hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy for patients with locally advanced recurrent nasopharyngeal carcinoma: A multicentre, randomised, open-label, phase 3 trial","volume":"401","author":"You","year":"2023","journal-title":"Lancet"},{"key":"ref_31","unstructured":"Network, N.C.C. (2025, April 16). NCCN Clinical Practice Guidelines in Oncology: Head and Neck Cancers. Available online: https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/head-and-neck.pdf."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Gong, L., Kwong, D.L., Dai, W., Wu, P., Wang, Y., Lee, A.W., and Guan, X.Y. (2021). The Stromal and Immune Landscape of Nasopharyngeal Carcinoma and Its Implications for Precision Medicine Targeting the Tumor Microenvironment. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.744889"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"S581","DOI":"10.1016\/j.annonc.2023.09.2064","article-title":"920P Envafolimab plus chemoradiotherapy for locally advanced nasopharyngeal carcinoma (NPC), a prospective, single-armed phase II trial","volume":"34","author":"Wang","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"S1554","DOI":"10.1016\/j.annonc.2024.10.424","article-title":"LBA3 First-line HLX07 vs. placebo combined with serplulimab and chemotherapy for nasopharyngeal cancer: A randomised, double-blind, multicentre phase II study","volume":"35","author":"Zhang","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Luo, J., Xiao, W., Hua, F., Cao, Y., Wang, D., and Wang, X. (2023). Efficacy and safety of PD-1 inhibitors in recurrent or metastatic nasopharyngeal carcinoma patients after failure of platinum-containing regimens: A systematic review and meta-analysis. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-11318-y"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1038\/s41590-019-0512-0","article-title":"Inhibitory receptors and ligands beyond PD-1, PD-L1 and CTLA-4: Breakthroughs or backups","volume":"20","author":"Andrews","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1200\/JCO.2024.42.16_suppl.3505","article-title":"Neoadjuvant treatment of IBI310 (anti-CTLA-4 antibody) plus sintilimab (anti-PD-1 antibody) in patients with microsatellite instability-high\/mismatch repair-deficient colorectal cancer: Results from a randomized, open-labeled, phase Ib study","volume":"42","author":"Xu","year":"2024","journal-title":"JCO"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13045-025-01666-6","article-title":"Anti-LAG-3 antibody LBL-007 plus anti-PD-1 antibody toripalimab in advanced nasopharyngeal carcinoma and other solid tumors: An open-label, multicenter, phase Ib\/II trial","volume":"18","author":"Chen","year":"2025","journal-title":"J. Hematol. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6033","DOI":"10.1200\/JCO.2024.42.16_suppl.6033","article-title":"Anti-LAG-3 antibody LBL-007 in combination with anti-PD-1 antibody tislelizumab with or without chemotherapy in patients with advanced nasopharyngeal cancer and other malignant tumors: A phase Ib\/II dose escalation\/expansion study","volume":"42","author":"Yang","year":"2024","journal-title":"JCO"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Andrzejczak, A., and Karabon, L. (2024). BTLA biology in cancer: From bench discoveries to clinical potentials. Biomark. Res., 12.","DOI":"10.1186\/s40364-024-00556-2"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1016\/j.ccell.2021.08.008","article-title":"Simultaneous targeting of TGF-\u03b2\/PD-L1 synergizes with radiotherapy by reprogramming the tumor microenvironment to overcome immune evasion","volume":"39","author":"Lan","year":"2021","journal-title":"Cancer Cell"},{"key":"ref_42","first-page":"100898","article-title":"Efficacy, safety, and correlative biomarkers of bintrafusp alfa in recurrent or metastatic nasopharyngeal cancer patients: A phase II clinical trial","volume":"40","author":"Chiang","year":"2023","journal-title":"Lancet Reg. Health\u2014West. Pac."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"S1559","DOI":"10.1016\/j.annonc.2024.10.439","article-title":"416P A study of AK104 (an anti-PD1 and anti-CTLA4 bispecific antibody) combined with chemotherapy for the treatment of anti-PD-1 resistant, recurrent, or metastatic nasopharyngeal carcinoma (R\/M NPC)","volume":"35","author":"Wen","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6026","DOI":"10.1200\/JCO.2024.42.16_suppl.6026","article-title":"Safety and efficacy of iparomlimab and tuvonralimab in combination with gemcitabine and cisplatin as first-line treatment for patients with recurrent or metastatic nasopharyngeal carcinoma: A multicenter, single-arm, phase 2 trial (DUBHE-N-302)","volume":"42","author":"Huang","year":"2024","journal-title":"JCO"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6034","DOI":"10.1200\/JCO.2022.40.16_suppl.6034","article-title":"Efficacy and safety of QL1706, a novel dual immune checkpoint blockade containing a mixture of anti-PD1 IgG4 and anti-CTLA4 IgG1 antibodies, for advanced nasopharyngeal carcinoma (NPC): Pooled cohort data from phase 1a\/1b trials","volume":"40","author":"Zhao","year":"2022","journal-title":"JCO"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13045-023-01445-1","article-title":"First-in-human phase I\/Ib study of QL1706 (PSB205), a bifunctional PD1\/CTLA4 dual blocker, in patients with advanced solid tumors","volume":"16","author":"Zhao","year":"2023","journal-title":"J. Hematol. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mascarelli, D.E., Rosa, R.S.M., Toscaro, J.M., Semionatto, I.F., Ruas, L.P., Fogagnolo, C.T., Lima, G.C., and Bajgelman, M.C. (2021). Boosting Antitumor Response by Costimulatory Strategies Driven to 4-1BB and OX40 T-cell Receptors. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.692982"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e005471","DOI":"10.1136\/jitc-2022-005471","article-title":"First-in-human study of an OX40 (ivuxolimab) and 4-1BB (utomilumab) agonistic antibody combination in patients with advanced solid tumors","volume":"10","author":"Hamid","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1128\/MCB.18.1.558","article-title":"4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor subfamily that bind TNF receptor-associated factors and activate nuclear factor kappaB","volume":"18","author":"Arch","year":"1998","journal-title":"Mol. Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"112270","DOI":"10.1016\/j.isci.2025.112270","article-title":"Anti-OX40 antibody BAT6026 in Patients with Advanced Solid Tumors: A Multi-Center Phase I Study","volume":"28","author":"Zhou","year":"2025","journal-title":"iScience"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"101414","DOI":"10.1016\/j.xcrm.2024.101414","article-title":"Preclinical characterization and phase 1 results of ADG106 in patients with advanced solid tumors and non-Hodgkin\u2019s lymphoma","volume":"5","author":"Ma","year":"2024","journal-title":"Cell Rep. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4049","DOI":"10.62347\/VYAT9271","article-title":"Metabolic reprogramming in the pathogenesis and progression of nasopharyngeal carcinoma: Molecular mechanisms and therapeutic implications","volume":"14","author":"Wang","year":"2024","journal-title":"Am. J. Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Su, Z.Y., Siak, P.Y., Leong, C.O., and Cheah, S.C. (2022). Nasopharyngeal Carcinoma and Its Microenvironment: Past, Current, and Future Perspectives. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.840467"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s12943-023-01733-x","article-title":"CD39\/CD73\/A2AR pathway and cancer immunotherapy","volume":"22","author":"Xia","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.neo.2017.02.004","article-title":"A Novel Antagonist of the Immune Checkpoint Protein Adenosine A2a Receptor Restores Tumor-Infiltrating Lymphocyte Activity in the Context of the Tumor Microenvironment","volume":"19","author":"Castro","year":"2017","journal-title":"Neoplasia"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"6380","DOI":"10.1158\/1538-7445.AM2025-6380","article-title":"Abstract 6380: PLX-4545, a selective IKZF2 degrader, reprograms suppressive Tregs leading to tumor growth inhibition and combination benefit with immune checkpoint therapy","volume":"85","author":"Huang","year":"2025","journal-title":"Cancer Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"CT150","DOI":"10.1158\/1538-7445.AM2025-CT150","article-title":"Abstract CT150: A first in humans trial of PLX-4545, a molecular glue degrader of IKZF2, in healthy volunteers, shows pharmacologic modulation of Tregs at well-tolerated doses","volume":"85","author":"DiMartino","year":"2025","journal-title":"Cancer Res."},{"key":"ref_58","first-page":"6952","article-title":"Immunization with Epstein-Barr Virus (EBV) peptide-pulsed dendritic cells induces functional CD8+ T-cell immunity and may lead to tumor regression in patients with EBV-positive nasopharyngeal carcinoma","volume":"62","author":"Lin","year":"2002","journal-title":"Cancer Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1007\/s00262-021-03075-3","article-title":"Dendritic cell therapy with CD137L-DC-EBV-VAX in locally recurrent or metastatic nasopharyngeal carcinoma is safe and confers clinical benefit","volume":"71","author":"Nickles","year":"2022","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1158\/0008-5472.CAN-12-2448","article-title":"Phase I trial of recombinant modified vaccinia ankara encoding Epstein-Barr viral tumor antigens in nasopharyngeal carcinoma patients","volume":"73","author":"Hui","year":"2013","journal-title":"Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5009","DOI":"10.1158\/1078-0432.CCR-14-1122-T","article-title":"A recombinant modified vaccinia ankara vaccine encoding Epstein-Barr Virus (EBV) target antigens: A phase I trial in UK patients with EBV-positive cancer","volume":"20","author":"Taylor","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Lin, M.C., Lin, Y.C., Chen, S.T., Young, T.H., and Lou, P.J. (2017). Therapeutic vaccine targeting Epstein-Barr virus latent protein, LMP1, suppresses LMP1-expressing tumor growth and metastasis in vivo. BMC Cancer, 17.","DOI":"10.1186\/s12885-016-3027-1"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"117","DOI":"10.5114\/ceji.2018.77379","article-title":"CD40L-adjuvanted DNA vaccine carrying EBV-LMP2 antigen enhances anti-tumor effect in NPC transplantation tumor animal","volume":"43","author":"Lei","year":"2018","journal-title":"Cent. Eur. J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1200\/JCO.2024.42.23_suppl.139","article-title":"Safety, tolerability, and immunogenicity of WGc-043 in subjects with EBV-positive cancers: Results from an investigator-initiated trial","volume":"42","author":"Peng","year":"2024","journal-title":"JCO"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"106083","DOI":"10.1016\/j.oraloncology.2022.106083","article-title":"Vaccination as a therapeutic strategy for Nasopharyngeal carcinoma","volume":"135","author":"Huang","year":"2022","journal-title":"Oral Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s12967-024-05880-7","article-title":"Unveiling immune resistance mechanisms in nasopharyngeal carcinoma and emerging targets for antitumor immune response: Tertiary lymphoid structures","volume":"23","author":"Wang","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Batista-Duharte, A., Hassouneh, F., Alvarez-Heredia, P., Pera, A., and Solana, R. (2022). Immune Checkpoint Inhibitors for Vaccine Improvements: Current Status and New Approaches. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14081721"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Albarr\u00e1n, V., San Rom\u00e1n, M., Pozas, J., Chamorro, J., Rosero, D.I., Guerrero, P., Calvo, J.C., Gonz\u00e1lez, C., Garc\u00eda de Quevedo, C., and P\u00e9rez de Aguado, P. (2024). Adoptive T cell therapy for solid tumors: Current landscape and future challenges. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1352805"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1093\/annonc\/mdh027","article-title":"Adoptive transfer of allogeneic Epstein\u2013Barr virus (EBV)-specific cytotoxic T cells with in vitro antitumor activity boostsLMP2-specific immune response in a patient with EBV-related nasopharyngeal carcinoma","volume":"15","author":"Comoli","year":"2004","journal-title":"Ann. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/S1044579X0200086X","article-title":"Epstein\u2013Barr virus in the pathogenesis of NPC","volume":"12","year":"2002","journal-title":"Semin. Cancer Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2642","DOI":"10.1002\/cncr.30541","article-title":"Epstein-Barr virus-specific adoptive immunotherapy for recurrent, metastatic nasopharyngeal carcinoma","volume":"123","author":"Huang","year":"2017","journal-title":"Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/j.annonc.2024.08.2344","article-title":"Gemcitabine, carboplatin, and Epstein-Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial","volume":"35","author":"Toh","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e1273311","DOI":"10.1080\/2162402X.2016.1273311","article-title":"Pre-emptive and therapeutic adoptive immunotherapy for nasopharyngeal carcinoma: Phenotype and effector function of T cells impact on clinical response","volume":"6","author":"Smith","year":"2017","journal-title":"OncoImmunology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"6096","DOI":"10.1200\/JCO.2024.42.16_suppl.6096","article-title":"Safety of tabelecleucel with pembrolizumab in recurrent\/metastatic Epstein\u2013Barr virus-associated nasopharyngeal carcinoma","volume":"42","author":"Colevas","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e976507","DOI":"10.4161\/23723556.2014.976507","article-title":"Phase I trial of adoptively transferred tumor-infiltrating lymphocyte immunotherapy following concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma","volume":"4","author":"Li","year":"2015","journal-title":"OncoImmunology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/nrclinonc.2016.36","article-title":"Driving CAR T-cells forward","volume":"13","author":"Jackson","year":"2016","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"eadg9721","DOI":"10.1126\/sciadv.adg9721","article-title":"EpCAM-targeting CAR-T cell immunotherapy is safe and efficacious for epithelial tumors","volume":"9","author":"Li","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1089\/hum.2020.283","article-title":"Generation of Epstein-Barr Virus Antigen-Specific T Cell Receptors Recognizing Immunodominant Epitopes of LMP1, LMP2A, and EBNA3C for Immunotherapy","volume":"32","author":"Dudaniec","year":"2021","journal-title":"Human Gene Ther."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Teppert, K., Wang, X., Anders, K., Evaristo, C., Lock, D., and K\u00fcnkele, A. (2022). Joining Forces for Cancer Treatment: From \u201cTCR versus CAR\u201d to \u201cTCR and CAR\u201d. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314563"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/nrd.2016.268","article-title":"Strategies and challenges for the next generation of antibody\u2013drug conjugates","volume":"16","author":"Beck","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/S0140-6736(19)31774-X","article-title":"Antibody\u2013drug conjugates for cancer","volume":"394","author":"Chau","year":"2019","journal-title":"Lancet"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Peng, X., Zhou, Y., Tao, Y., and Liu, S. (2021). Nasopharyngeal Carcinoma: The Role of the EGFR in Epstein-Barr Virus Infection. Pathogens, 10.","DOI":"10.3390\/pathogens10091113"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Wang, L., Zhuang, H., Xu, X., Zhou, J., and Jiao, Y. (2023). Efficacy and survival analysis of nimotuzumab combined with concurrent chemoradiotherapy in the treatment of locally advanced nasopharyngeal carcinoma. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1129649"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"LBA6005","DOI":"10.1200\/JCO.2025.43.17_suppl.LBA6005","article-title":"Becotatug vedotin vs. chemotherapy in pre-heavily treated advanced nasopharyngeal carcinoma: A randomized, controlled, multicenter, open-label study","volume":"43","author":"Han","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13046-021-02215-y","article-title":"The CD70-CD27 axis in oncology: The new kids on the block","volume":"41","author":"Flieswasser","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Garmezy, B., Kambhampati, S., Curti, B., Reimers, M., Caimi, P., Diefenbach, C., Heath, E., Jonasch, E., Park, S., and Kornblum, N. (2023, January 1\u20135). 718 Phase 1\/2 study of PRO1160, a CD70-directed antibody-drug conjugate, in patients with advanced solid tumors and hematologic malignancies. Proceedings of the SITC 38th Annual Meeting (SITC 2023) Abstracts, San Diego, CA, USA.","DOI":"10.1136\/jitc-2023-SITC2023.0718"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1038\/s41591-025-03600-2","article-title":"A B7H3-targeting antibody\u2013drug conjugate in advanced solid tumors: A phase 1\/1b trial","volume":"31","author":"Ma","year":"2025","journal-title":"Nat. Med."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Chen, Q., Jia, G., Zhang, X., and Ma, W. (2024). Targeting HER3 to overcome EGFR TKI resistance in NSCLC. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1332057"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/S1470-2045(24)00159-1","article-title":"BL-B01D1, a first-in-class EGFR\u2013HER3 bispecific antibody\u2013drug conjugate, in patients with locally advanced or metastatic solid tumours: A first-in-human, open-label, multicentre, phase 1 study","volume":"25","author":"Ma","year":"2024","journal-title":"Lancet Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1038\/onc.2013.57","article-title":"AXL induces epithelial-to-mesenchymal transition and regulates the function of breast cancer stem cells","volume":"33","author":"Asiedu","year":"2014","journal-title":"Oncogene"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1073274821989301","DOI":"10.1177\/1073274821989301","article-title":"Nimotuzumab, an Anti-EGFR Monoclonal Antibody, in the Treatment of Nasopharyngeal Carcinoma","volume":"28","author":"Liang","year":"2021","journal-title":"Cancer Control"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Wang, R.-J., Ke, R.-Q., Yu, Y.-F., Lu, G.-Z., and Wu, S.-G. (2024). Addition of nimotuzumab to concurrent chemoradiotherapy after induction chemotherapy improves outcomes of patients with locally advanced nasopharyngeal carcinoma. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1366853"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Bourhis, M., Palle, J., Galy-Fauroux, I., and Terme, M. (2021). Direct and Indirect Modulation of T Cells by VEGF-A Counteracted by Anti-Angiogenic Treatment. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.616837"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"102136","DOI":"10.1016\/j.eclinm.2023.102136","article-title":"Efficacy and safety of sintilimab plus bevacizumab in metastatic nasopharyngeal carcinoma after failure of platinum-based chemotherapy: An open-label phase 2 study","volume":"62","author":"Lu","year":"2023","journal-title":"EClinicalMedicine"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4893","DOI":"10.1038\/s41467-023-40402-x","article-title":"Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent\/metastatic nasopharyngeal carcinoma: A single-arm, phase 2 trial","volume":"14","author":"Yuan","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1158\/2159-8290.CD-17-0915","article-title":"CDK4\/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation","volume":"8","author":"Deng","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"S633","DOI":"10.1016\/j.annonc.2024.08.953","article-title":"892P Camrelizumab plus dalpiciclib in anti-PD-1 refractory recurrent or metastatic nasopharyngeal carcinoma","volume":"35","author":"Ding","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"S633","DOI":"10.1016\/j.annonc.2024.08.952","article-title":"891P Pembrolizumab and olaparib in recurrent\/metastatic, platinum resistant nasopharyngeal cancer: The POINT study","volume":"35","author":"Gurizzan","year":"2024","journal-title":"Ann. Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"S1607","DOI":"10.1016\/j.annonc.2023.10.462","article-title":"354O A phase Ib\/II study of nanatinostat (Nstat) plus valganciclovir (VGCV) in EBV+ solid tumors and with pembrolizumab (PEM) in recurrent\/metastatic nasopharyngeal carcinoma (R\/M NPC)","volume":"34","author":"Colevas","year":"2023","journal-title":"Ann. Oncol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"6339","DOI":"10.1182\/bloodadvances.2023010330","article-title":"Targeted therapy with nanatinostat and valganciclovir in recurrent EBV-positive lymphoid malignancies: A phase 1b\/2 study","volume":"7","author":"Haverkos","year":"2023","journal-title":"Blood Adv."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"13958","DOI":"10.1002\/cam4.6011","article-title":"The expanding role of IAP antagonists for the treatment of head and neck cancer","volume":"12","author":"Kansal","year":"2023","journal-title":"Cancer Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"6035","DOI":"10.1200\/JCO.2023.41.16_suppl.6035","article-title":"Phase I\/IIa clinical trial of a small molecule EBNA1 inhibitor, VK-2019, in patients with Epstein Barr virus\u2013positive nasopharyngeal cancer with pharmacokinetic and pharmacodynamic correlative studies","volume":"41","author":"Colevas","year":"2023","journal-title":"JCO"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Sugiokto, F.G., and Li, R. (2025). Targeting EBV Episome for Anti-Cancer Therapy: Emerging Strategies and Challenges. Viruses, 17.","DOI":"10.3390\/v17010110"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Suryani, L., Lee, H.P.Y., Teo, W.K., Chin, Z.K., Loh, K.S., and Tay, J.K. (2024). Precision Medicine for Nasopharyngeal Cancer-A Review of Current Prognostic Strategies. Cancers, 16.","DOI":"10.3390\/cancers16050918"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Liu, X., Li, Y., Zhou, X., Zhu, S., Kaya, N.A., Chan, Y.S., Ma, L., Xu, M., and Zhai, W. (2023). An Integrative Analysis of Nasopharyngeal Carcinoma Genomes Unraveled Unique Processes Driving a Viral-Positive Cancer. Cancers, 15.","DOI":"10.3390\/cancers15041243"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1038\/ng.3006","article-title":"The genomic landscape of nasopharyngeal carcinoma","volume":"46","author":"Lin","year":"2014","journal-title":"Nat. Genet."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Peng, H., Chen, L., Chen, Y.-P., Li, W.-F., Tang, L.-L., Lin, A.-H., Sun, Y., and Ma, J. (2018). The current status of clinical trials focusing on nasopharyngeal carcinoma: A comprehensive analysis of ClinicalTrials.gov database. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0196730"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1097\/CM9.0000000000003371","article-title":"Efficacy and safety of immune checkpoint inhibitors in the treatment of recurrent or metastatic nasopharyngeal carcinoma: A systematic review and meta-analysis","volume":"138","author":"Yu","year":"2024","journal-title":"Chin. Med. J."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1007\/s00405-021-06922-2","article-title":"The global burden of nasopharyngeal carcinoma from 2009 to 2019: An observational study based on the Global Burden of Disease Study 2019","volume":"279","author":"Yu","year":"2022","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.ejca.2021.09.005","article-title":"Nasopharyngeal cancer in non-endemic areas: Impact of treatment intensity within a large retrospective multicentre cohort","volume":"159","author":"Bossi","year":"2021","journal-title":"Eur. J. Cancer"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Xu, R., Wong, C.H.L., Chan, K.S.K., and Chiang, C.L. (2024). PD-L1 expression as a potential predictor of immune checkpoint inhibitor efficacy and survival in patients with recurrent or metastatic nasopharyngeal cancer: A systematic review and meta-analysis of prospective trials. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1386381"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Economopoulou, P., Pantazopoulos, A., Spathis, A., Kotsantis, I., Kyriazoglou, A., Kavourakis, G., Zakopoulou, R., Chatzidakis, I., Anastasiou, M., and Prevezanou, M. (2021). Immunotherapy in Nonendemic Nasopharyngeal Carcinoma: Real-World Data from Two Nonendemic Regions. Cells, 11.","DOI":"10.3390\/cells11010032"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1016\/j.annonc.2023.08.008","article-title":"Treatment of evolving cancers will require dynamic decision support","volume":"34","author":"Strobl","year":"2023","journal-title":"Ann. Oncol."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/32\/9\/479\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:32:59Z","timestamp":1760034779000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/32\/9\/479"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,26]]},"references-count":113,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["curroncol32090479"],"URL":"https:\/\/doi.org\/10.3390\/curroncol32090479","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,26]]}}}