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%. Here we report high somatostatin receptor 2 expression in multiple clinical cohorts comprising 402 primary, locally recurrent and metastatic NPCs. We show that 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 duanyu1942R2 targeting using a cytotoxic drug conjugate, PEN-221, which is found to be superior to FDA-approved cytostatic agents. Furthermore, we reveal significant correlation of expression with increased rates of survival and report in vivo uptake of the duanyu1942R2-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 duanyu1942R2 in infection, imaging, targeted therapy and survival.

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