期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-020-20308-8
关键词
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资金
- Rhinology and Laryngology Research Fund
- Royal College of Surgeons (Colledge Family Research Grant)
- UCL/UCLH Biomedical Research Centre (BRC)
- Association for the Global Advancement of ENT Surgery and Head and Neck Cancer Research (AGA-ENT)
- Austrian Science Foundation (FWF) [I 3976-B33]
- Christian Doppler Research Association
- ASEAN-European Academic University Network (ASEA-UNINET)
- Austrian Federal Ministry of Education, Science and Research
- Austrian Agency for International Cooperation in Education and Research (OeAD-GmbH)
- Cancer Research UK [C23338/A25722]
- UK NIHR University College London Hospitals Biomedical Research Centre
- Cancer Research UK clinician scientist fellowship [18387]
- Cancer Research UK
- National Medical Research Council Singapore Clinician-Scientist Award [NMRC/CSA/0027/2018]
- Duke-NUS Oncology Academic Program Proton Research Program
- National Research Foundation Clinical Research Program Grant [NRF-CRP17-2017-05]
- National Medical Research Council Singapore Research Training Fellowship
- National Cancer Center Singapore Research Fund
- LEAN Network from the Leducq Foundation
- NIHR BRC Oxford
- CRUK
- People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA [609305]
- NIDCR/NIH [R01 DE025227]
- Research Grants Council (RGC) of Hong Kong [T1-2-401/13-R, C4001-18GF, 14117316, C7027-16G, C5012-15E]
- [GRF 106180141]
- [CRF C7027-16G]
- [HRF260870784]
This study reveals that somatostatin receptor 2 is induced by the Epstein-Barr virus in nasopharyngeal carcinoma and plays a key role in the diagnosis, imaging, targeted therapies, and prognosis of the disease.
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-kappa B 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 Ga-68-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. Nasopharyngeal carcinoma (NPC) lacks effective diagnostic and therapeutic strategies, in particular at advanced stages. Here, the authors show that expression of the somatostatin receptor 2 is induced by Epstein-Barr virus in NPC and has a key role in the diagnosis, imaging, targeted therapies and prognosis of NPC.
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