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

Matt Lechner (), Volker H. 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, Julia Koller, Susanne Delecluse, Yim Ling Yip, Jacklyn Liu, Cillian T. Forde, Martin D. Forster, 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 S. H. 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 () and Valerie J. Lund ()
Additional contact information
Matt Lechner: University College London
Volker H. Schartinger: Medical University of Innsbruck
Christopher D. Steele: University College London
Wen Long Nei: National Cancer Centre
Marc Lucas Ooft: NHS Foundation Trust
Liesa-Marie Schreiber: Medical University of Innsbruck
Christodoulos P. Pipinikas: University College London
Grace Tin-Yun Chung: The Chinese University of Hong Kong
Yuk Yu Chan: The Chinese University of Hong Kong
Feng Wu: The Chinese University of Hong Kong
Ka-Fai To: The Chinese University of Hong Kong
Chi Man Tsang: The Chinese University of Hong Kong
Wayne Pearce: University College London
Daniele Morelli: University College London
Martin Philpott: University of Oxford
Liam Masterson: Addenbrooke’s Hospital
Reshma Nibhani: University of Oxford
Graham Wells: University of Oxford
Christopher G. Bell: Queen Mary University of London
Julia Koller: Medical University of Innsbruck
Susanne Delecluse: German Cancer Research Centre (DKFZ) and Inserm, Unit F100/U1074
Yim Ling Yip: University of Hong Kong
Jacklyn Liu: University College London
Cillian T. Forde: University College London Hospitals NHS Trust
Martin D. Forster: University College London
Amrita Jay: University College London Hospitals NHS Trust
József Dudás: Medical University of Innsbruck
Annika Krapp: Medical University of Innsbruck
Simon Wan: University College Hospital
Christian Uprimny: Medical University of Innsbruck
Susanne Sprung: Medical University of Innsbruck
Johannes Haybaeck: Medical University of Innsbruck
Tim R. Fenton: University of Kent
Kerry Chester: University College London
Christina Thirlwell: University College London
Gary Royle: University College London
Teresa Marafioti: University College London
Rajeev Gupta: University College London
Sagung Rai Indrasari: Universitas Gadjah Mada, Dr. Sardjito Hospital
Camelia Herdini: Universitas Gadjah Mada, Dr. Sardjito Hospital
Mohd Afiq Mohd Slim: University Hospital Crosshouse
I. Indrawati: Universitas Gadjah Mada, Dr. Sardjito Hospital
Liam Sutton: Barts Health NHS Trust
Renske Fles: Netherlands Cancer Institute
Bing Tan: Universitas Gadjah Mada, Dr. Sardjito Hospital
Joe Yeong: Singapore General Hospital
Amit Jain: National Cancer Centre
Shuting Han: National Cancer Centre
Haitao Wang: National Cancer Centre
Kelvin S. H. Loke: Singapore General Hospital
Wan He: Jinan University
Ruilian Xu: Jinan University
Hongtao Jin: Jinan University
Zhiqiang Cheng: Jinan University
David Howard: University College London Hospitals NHS Trust
Peter H. Hwang: Stanford University School of Medicine
Quynh-Thu Le: Stanford University School of Medicine
Joshua K. Tay: Stanford University School of Medicine
Robert B. West: Stanford University School of Medicine
Sai Wah Tsao: University of Hong Kong
Tim Meyer: University College London
Herbert Riechelmann: Medical University of Innsbruck
Udo Oppermann: University of Oxford
Henri-Jacques Delecluse: German Cancer Research Centre (DKFZ) and Inserm, Unit F100/U1074
Stefan M. Willems: University Medical Center Utrecht
Melvin L. K. Chua: National Cancer Centre
Pierre Busson: CNRS-UMR 9018-METSY, Gustave Roussy and Université Paris-Saclay
Kwok Wai Lo: The Chinese University of Hong Kong
Guido Wollmann: Medical University of Innsbruck
Nischalan Pillay: University College London
Bart Vanhaesebroeck: University College London
Valerie J. Lund: University College London

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-020-20308-8

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