Portal de Periódicos da CAPES

Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy

2021; Nature Portfolio; Volume: 12; Issue: 1 Linguagem: Inglês

10.1038/s41467-020-20308-8

2041-1723

Matt Lechner, Volker Hans Schartinger, Christopher D. Steele, Wen Long Nei, Marc Lucas Ooft, Liesa-Marie Schreiber, Christodoulos P. Pipinikas, Grace Tin‐Yun Chung, Yuk Yu Chan, Feng Wu, Ka‐Fai To, Chi Man Tsang, Wayne Pearce, Daniele Morelli, Martin Philpott, Liam Masterson, Reshma Nibhani, Graham Wells, Christopher G. Bell, Júlia Koller, Susanne Delécluse, Yim Ling Yip, Jacklyn Liu, Cillian T. Forde, Martin Förster, Amrita Jay, József Dudás, Annika Krapp, Simon Wan, Christian Uprimny, Susanne Sprung, Johannes Haybaeck, Tim R. Fenton, Kerry Chester, Christina Thirlwell, Gary Royle, Teresa Marafioti, Rajeev Gupta, Sagung Rai Indrasari, Camelia Herdini, Mohd Afiq Mohd Slim, I. Indrawati, Liam Sutton, Renske Fles, Bing Tan, Joe Yeong, Amit Jain, Shuting Han, Haitao Wang, Kelvin Siu Hoong Loke, Wan He, Ruilian Xu, Hongtao Jin, Zhiqiang Cheng, David Howard, Peter H. Hwang, Quynh‐Thu Le, Joshua K. Tay, Robert B. West, Sai Wah Tsao, Tim Meyer, Herbert Riechelmann, Udo Oppermann, Henri‐Jacques Delecluse, Stefan M. Willems, Melvin L.K. Chua, Pierre Busson, Kwok Wai Lo, Guido Wollmann, Nischalan Pillay, Bart Vanhaesebroeck, Valerie J. Lund,

Fibroblast Growth Factor Research

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 68 Ga-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.