| Literature DB >> 33402692 |
Matt Lechner1,2,3,4, Volker H Schartinger5, Christopher D Steele6, Wen Long Nei7,8, Marc Lucas Ooft9,10, Liesa-Marie Schreiber11, Christodoulos P Pipinikas6, Grace Tin-Yun Chung12, Yuk Yu Chan12, Feng Wu12, Ka-Fai To12, Chi Man Tsang12, Wayne Pearce6, Daniele Morelli6, Martin Philpott13, Liam Masterson14, Reshma Nibhani13, Graham Wells13, Christopher G Bell15, Julia Koller5,13, Susanne Delecluse16, Yim Ling Yip17, Jacklyn Liu6, Cillian T Forde18, Martin D Forster6,18, Amrita Jay19, József Dudás5, Annika Krapp5, Simon Wan20, Christian Uprimny21, Susanne Sprung22, Johannes Haybaeck22,23, Tim R Fenton24, Kerry Chester6, Christina Thirlwell6,25, Gary Royle6, Teresa Marafioti6, Rajeev Gupta6, Sagung Rai Indrasari26, Camelia Herdini26, Mohd Afiq Mohd Slim27, I Indrawati28, Liam Sutton29, Renske Fles30, Bing Tan26,31, Joe Yeong32,33, Amit Jain34, Shuting Han34, Haitao Wang7, Kelvin S H Loke35, Wan He36, Ruilian Xu36, Hongtao Jin37, Zhiqiang Cheng37, David Howard18,38, Peter H Hwang39, Quynh-Thu Le40, Joshua K Tay41,42, Robert B West41, Sai Wah Tsao17, Tim Meyer6, Herbert Riechelmann5, Udo Oppermann13,43, Henri-Jacques Delecluse16, Stefan M Willems10,44, Melvin L K Chua7,8, Pierre Busson45, Kwok Wai Lo12, Guido Wollmann11, Nischalan Pillay6,46, Bart Vanhaesebroeck47, Valerie J Lund48,49.
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.Entities:
Mesh：
Substances：
Year: 2021 PMID： 33402692 PMCID： PMC7785735 DOI： 10.1038/s41467-020-20308-8
Source DB: PubMed Journal: Nat Commun ISSN： 2041-1723 Impact factor: 14.919