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

Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy
Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy
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 (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 68Ga-DOTA-peptide radio-conjugate 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.
2041-1723
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Schartinger, VH
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Tsang, CM
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Pearce, W
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Marafioti, Teresa
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Gupta, R
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Pillay, N
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Lund, VJ
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Lechner, M, Schartinger, VH, Steele, CD, Nei, WL, Ooft, ML, Schreiber, L-M, Pipinikas, CP, Chung, G T-Y, Chan, YY, Wu, F, To, K-F, Tsang, CM, Pearce, W, Morelli, D, Philpott, M, Masterson, L, Ribhani, R, Wells, G, Bell, C, Koller, J, Delacuse, S, Yip, YL, Liu, J, Forde, CT, Forster, MD, Jay, A, Dudas, J, Krapp, A, Wan, S, Uprimny, C, Sprung, S, Haybaeck, J, Fenton, TR, Chester, K, Thirlwell, C, Royle, G, Marafioti, Teresa, Gupta, R, Indrasari, SR, Herdini, C, Slim, MAM, Indrawati, I, Sutton, L, Fles, R, Tang, B, Yeong, J, Jain, A, Han, S, Wang, H, Loke, KSH, He, W, Xu, R, Jin, Hongtao, Cheng, Z, Howard, D, Hwang, PH, Le, Q-T, Tay, JK, West, RB, Tsao, SW, Meyer, T, Riechelmann, H, Oppermann, U, Delecuse, H-J, Willems, SW, Chua, MLK, Busson, P, Lo, KW, Wollmann, G, Pillay, N, Vanhaesebroeck, B and Lund, VJ (2021) Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy. Nature Communications, 12, [117]. (doi:10.1038/s41467-020-20308-8).

Record type: Article

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 (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 68Ga-DOTA-peptide radio-conjugate 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.

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More information

Accepted/In Press date: 17 November 2020
Published date: 5 January 2021
Learn more about School of Chemistry research Learn more about Engineering Sciences research Learn more about School of Electronics and Computer Science research Learn more about School of Biological Sciences research Learn more about Ocean and Earth Science research Learn more about Electronics & Computer Science research

Identifiers

Local EPrints ID: 453961
URI: http://eprints.soton.ac.uk/id/eprint/453961
DOI: doi:10.1038/s41467-020-20308-8
ISSN: 2041-1723
PURE UUID: febcf341-e991-40df-b0e7-b6c2737cc4c2
ORCID for TR Fenton: ORCID iD orcid.org/0000-0002-4737-8233

Catalogue record

Date deposited: 26 Jan 2022 17:50
Last modified: 17 Mar 2024 04:11

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Contributors

Author: M Lechner
Author: VH Schartinger
Author: CD Steele
Author: WL Nei
Author: ML Ooft
Author: L-M Schreiber
Author: CP Pipinikas
Author: G T-Y Chung
Author: YY Chan
Author: F Wu
Author: K-F To
Author: CM Tsang
Author: W Pearce
Author: D Morelli
Author: M Philpott
Author: L Masterson
Author: R Ribhani
Author: G Wells
Author: C Bell
Author: J Koller
Author: S Delacuse
Author: YL Yip
Author: J Liu
Author: CT Forde
Author: MD Forster
Author: A Jay
Author: J Dudas
Author: A Krapp
Author: S Wan
Author: C Uprimny
Author: S Sprung
Author: J Haybaeck
Author: TR Fenton ORCID iD
Author: K Chester
Author: C Thirlwell
Author: G Royle
Author: Teresa Marafioti
Author: R Gupta
Author: SR Indrasari
Author: C Herdini
Author: MAM Slim
Author: I Indrawati
Author: L Sutton
Author: R Fles
Author: B Tang
Author: J Yeong
Author: A Jain
Author: S Han
Author: H Wang
Author: KSH Loke
Author: W He
Author: R Xu
Author: Hongtao Jin
Author: Z Cheng
Author: D Howard
Author: PH Hwang
Author: Q-T Le
Author: JK Tay
Author: RB West
Author: SW Tsao
Author: T Meyer
Author: H Riechelmann
Author: U Oppermann
Author: H-J Delecuse
Author: SW Willems
Author: MLK Chua
Author: P Busson
Author: KW Lo
Author: G Wollmann
Author: N Pillay
Author: B Vanhaesebroeck
Author: VJ Lund

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