Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-020-20308-8
Title: Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy
Authors: Lechner, Matt
Schartinger, Volker H.
Steele, Christopher D.
Nei, Wen Long
Ooft, Marc Lucas
Schreiber, Liesa-Marie
Pipinikas, Christodoulos P.
Chung, Grace Tin-Yun
Chan, Yuk Yu
Wu, Feng
To, Ka-Fai
Tsang, Chi Man
Pearce, Wayne
Morelli, Daniele
Philpott, Martin
Masterson, Liam
Nibhani, Reshma
Wells, Graham
Bell, Christopher G.
Koller, Julia
Delecluse, Susanne
Yip, Yim Ling
Liu, Jacklyn
Forde, Cillian T.
Forster, Martin D.
Jay, Amrita
Dudás, József
Krapp, Annika
Wan, Simon
Uprimny, Christian
Sprung, Susanne
Haybaeck, Johannes
Fenton, Tim R.
Chester, Kerry
Thirlwell, Christina
Royle, Gary
Marafioti, Teresa
Gupta, Rajeev
Indrasari, Sagung Rai
Herdini, Camelia
Slim, Mohd Afiq Mohd
Indrawati, I.
Sutton, Liam
Fles, Renske
Tan, Bing
Yeong, Joe
Jain, Amit
Han, Shuting
Wang, Haitao
Loke, Kelvin S. H.
He, Wan
Xu, Ruilian
Jin, Hongtao
Cheng, Zhiqiang
Howard, David
Hwang, Peter H.
Le, Quynh-Thu
Tay, Joshua K. 
West, Robert B.
Tsao, Sai Wah
Meyer, Tim
Riechelmann, Herbert
Oppermann, Udo
Delecluse, Henri-Jacques
Willems, Stefan M.
Chua, Melvin L. K. 
Busson, Pierre
Lo, Kwok Wai
Wollmann, Guido
Pillay, Nischalan
Vanhaesebroeck, Bart
Lund, Valerie J.
Issue Date: 5-Jan-2021
Publisher: Nature Research
Citation: Lechner, Matt, Schartinger, Volker H., Steele, Christopher D., Nei, Wen Long, Ooft, Marc Lucas, Schreiber, Liesa-Marie, Pipinikas, Christodoulos P., Chung, Grace Tin-Yun, Chan, Yuk Yu, Wu, Feng, To, Ka-Fai, Tsang, Chi Man, Pearce, Wayne, Morelli, Daniele, Philpott, Martin, Masterson, Liam, Nibhani, Reshma, Wells, Graham, Bell, Christopher G., Koller, Julia, Delecluse, Susanne, Yip, Yim Ling, Liu, Jacklyn, Forde, Cillian T., Forster, Martin D., Jay, Amrita, Dudás, József, Krapp, Annika, Wan, Simon, Uprimny, Christian, Sprung, Susanne, Haybaeck, Johannes, Fenton, Tim R., Chester, Kerry, Thirlwell, Christina, Royle, Gary, Marafioti, Teresa, Gupta, Rajeev, Indrasari, Sagung Rai, Herdini, Camelia, Slim, Mohd Afiq Mohd, Indrawati, I., Sutton, Liam, Fles, Renske, Tan, Bing, Yeong, Joe, Jain, Amit, Han, Shuting, Wang, Haitao, Loke, Kelvin S. H., He, Wan, Xu, Ruilian, Jin, Hongtao, Cheng, Zhiqiang, Howard, David, Hwang, Peter H., Le, Quynh-Thu, Tay, Joshua K., West, Robert B., Tsao, Sai Wah, Meyer, Tim, Riechelmann, Herbert, Oppermann, Udo, Delecluse, Henri-Jacques, Willems, Stefan M., Chua, Melvin L. K., Busson, Pierre, Lo, Kwok Wai, Wollmann, Guido, Pillay, Nischalan, Vanhaesebroeck, Bart, Lund, Valerie J. (2021-01-05). Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy. Nature Communications 12 (1) : 117. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-020-20308-8
Rights: Attribution 4.0 International
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-?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 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. © 2021, The Author(s).
Source Title: Nature Communications
URI: https://scholarbank.nus.edu.sg/handle/10635/233091
ISSN: 2041-1723
DOI: 10.1038/s41467-020-20308-8
Rights: Attribution 4.0 International
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