Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Lechner, M; Schartinger, VH; Steele, CD; Nei, WL; Ooft, ML; Schreiber, LM; Pipinikas, CP; Chung, GT; Chan, YY; Wu, F; To, KF; Tsang, CM; Pearce, W; Morelli, D; Philpott, M; Masterson, L; Nibhani, R; Wells, G; Bell, CG; Koller, J; Delecluse, S; Yip, YL; Liu, J; Forde, CT; Forster, MD; Jay, A; Dudás, J; Krapp, A; Wan, S; Uprimny, C; Sprung, S; Haybaeck, J; Fenton, TR; Chester, K; Thirlwell, C; Royle, G; Marafioti, T; Gupta, R; Indrasari, SR; Herdini, C; Slim, MAM; Indrawati, I; Sutton, L; Fles, R; Tan, B; Yeong, J; Jain, A; Han, S; Wang, H; Loke, KSH; He, W; Xu, R; Jin, H; Cheng, Z; Howard, D; Hwang, PH; Le, QT; Tay, JK; West, RB; Tsao, SW; Meyer, T; Riechelmann, H; Oppermann, U; Delecluse, HJ; Willems, SM; Chua, MLK; Busson, P; Lo, KW; Wollmann, G; Pillay, N; Vanhaesebroeck, B; Lund, VJ.
Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy.
Nat Commun. 2021; 12(1): 117-117.
Doi: 10.1038/s41467-020-20308-8
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- Co-Autor*innen der Med Uni Graz
- Haybäck Johannes
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- Abstract:
- 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 rates of survival and report in vivo uptake of the SSTR2-binding 68Ga-DOTA-peptide radioconjugate in PET-CT scanning in a clinical trial of NPC patients (NCT03670342). These findings reveal a key role in EBV-associated NPC for SSTR2 in infection, imaging, targeted therapy and survival.