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

Lechner, M, Schartinger, VH, Steele, CD, Nei, WL, Ooft, ML, Schreiber, L-M, Pipinikas, CP, Chung, G T-Y, Chan, YY, Wu, F, and others. (2021) Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy. Nature Communications, 12 . Article Number 117. ISSN 2041-1723. (doi:10.1038/s41467-020-20308-8) (KAR id:85329)

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Official URL: https://www.nature.com/articles/s41467-020-20308-8

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 EBVassociated NPC for SSTR2 in infection, imaging, targeted therapy and survival.

Item Type:	Article
DOI/Identification number:	10.1038/s41467-020-20308-8
Divisions:	Divisions > Division of Natural Sciences > Biosciences
Depositing User:	Tim Fenton
Date Deposited:	05 Jan 2021 17:58 UTC
Last Modified:	05 Nov 2024 12:51 UTC
Resource URI:	https://kar.kent.ac.uk/id/eprint/85329 (The current URI for this page, for reference purposes)

University of Kent Author Information

Fenton, TR.

Creator's ORCID:	https://orcid.org/0000-0002-4737-8233
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