biostudies-literatureLechner MAustrian Science Fund FWFCancer Research UKNIDCR NIH HHSVersus ArthritisNational Institute for Health Research (NIHR)RosetreesWellcome Trust117https://www.ebi.ac.uk/biostudies/studies/S-EPMC7785735biostudies-literatureUnknown12(1)Nasopharyngeal cancer (NPC), endemic in Southeast Asia, lacks effective diagnostic and therapeutic strategies. Even in high-income countries the 5-year survival rate for stage IV NPC is less than 40%. Here we report high somatostatin receptor 2 (SSTR2) expression in multiple clinical cohorts comprising 402 primary, locally recurrent and metastatic NPCs. We show that SSTR2 expression is induced by the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) via the NF-κB pathway. Using cell-based and preclinical rodent models, we demonstrate the therapeutic potential of SSTR2 targeting using a cytotoxic drug conjugate, PEN-221, which is found to be superior to FDA-approved SSTR2-binding cytostatic agents. Furthermore, we reveal significant correlation of SSTR expression with increased rateNature communicationsSomatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy.PMC778573523900I 397620522M229-CD1C23338/A25722I 3976-B33R01 DE025227183872572215965Wan SWest RBTsao SWPipinikas CPOppermann UPillay NPhilpott MUprimny CWang HWu FSutton LWells GMarafioti TJain AJin HMeyer TNibhani RRoyle GNei WLLoke KSHSteele CDFenton TRSchartinger VHKoller JXu RYip YLSlim MAMThirlwell CTan BTay JKPearce WMasterson LHe WChua MLKIndrasari SRWollmann GLiu JHoward DMorelli DSprung SForster MDSchreiber LMChan YYHan SCheng ZTo KFDudas JFles RYeong JLe QTBell CGKrapp ATsang CMGupta RJay AHerdini CLo KWLund VJLechner MBusson PHwang PHChester KHaybaeck JRiechelmann HWillems SMIndrawati IOoft MLForde CTDelecluse HJDelecluse SChung GTVanhaesebroeck BfalseSomatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy.Nasopharyngeal cancer (NPC), endemic in Southeast Asia, lacks effective diagnostic and therapeutic strategies. Even in high-income countries the 5-year survival rate for stage IV NPC is less than 40%. Here we report high somatostatin receptor 2 (SSTR2) expression in multiple clinical cohorts comprising 402 primary, locally recurrent and metastatic NPCs. We show that SSTR2 expression is induced by the Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) via the NF-κB pathway. Using cell-based and preclinical rodent models, we demonstrate the therapeutic potential of SSTR2 targeting using a cytotoxic drug conjugate, PEN-221, which is found to be superior to FDA-approved SSTR2-binding cytostatic agents. Furthermore, we reveal significant correlation of SSTR expression with increased rate2021-01-01T00:00:00Z2021 Jan2026-04-30T16:28:59.325Z2024-11-09T11:45:34.675ZS-EPMC77857353340269210.1038/s41467-020-20308-8