Nature communications · 2021

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

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен

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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

Аннотация

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.

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

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