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.
复制标题
DOI：
10.1038/s41467-020-20308-8
复制
发表时间：
2021-01-05
影响因子：
16.6
通讯作者：
Lund VJ
中科院分区：
文献类型：
--
作者：
Lechner M;Schartinger VH;Steele CD;Nei WL;Ooft ML;Schreiber LM;Pipinikas CP;Chung GT;Chan YY;Wu F;To KF;Tsang CM;Pearce W;Morelli D;Philpott M;Masterson L;Nibhani R;Wells G;Bell CG;Koller J;Delecluse S;Yip YL;Liu J;Forde CT;Forster MD;Jay A;Dudás J;Krapp A;Wan S;Uprimny C;Sprung S;Haybaeck J;Fenton TR;Chester K;Thirlwell C;Royle G;Marafioti T;Gupta R;Indrasari SR;Herdini C;Slim MAM;Indrawati I;Sutton L;Fles R;Tan B;Yeong J;Jain A;Han S;Wang H;Loke KSH;He W;Xu R;Jin H;Cheng Z;Howard D;Hwang PH;Le QT;Tay JK;West RB;Tsao SW;Meyer T;Riechelmann H;Oppermann U;Delecluse HJ;Willems SM;Chua MLK;Busson P;Lo KW;Wollmann G;Pillay N;Vanhaesebroeck B;Lund VJ
鼻咽癌是东南亚的一种地方性疾病，缺乏有效的诊断和治疗策略。即使在高收入国家，四期鼻咽癌的五年存活率也不到40%。在这里，我们报告了生长抑素受体2(SSTR2)在包括402例原发、局部复发和转移的鼻咽癌的多个临床队列中的高表达。我们发现SSTR2的表达是由EB病毒潜伏膜蛋白1(LMP1)通过NF-κB途径诱导的。使用基于细胞的和临床前啮齿动物模型，我们证明了使用细胞毒性药物结合物PEN-221靶向SSTR2的治疗潜力，该药物被发现优于FDA批准的结合SSTR2的细胞抑制剂。此外，我们发现SSTR的表达与鼻咽癌患者存活率的增加显著相关，并在一项鼻咽癌患者的临床试验(NCT03670342)中报告了在PET-CT扫描中SSTR2结合的68Ga-DOTA多肽放射性结合物的体内摄取。这些发现揭示了SSTR2在EB病毒相关性鼻咽癌的感染、成像、靶向治疗和生存中的关键作用。鼻咽癌(NPC)缺乏有效的诊断和治疗策略，尤其是在晚期。作者认为，生长抑素受体2在鼻咽癌中的表达是由EB病毒诱导的，在鼻咽癌的诊断、成像、靶向治疗和预后中起着关键作用。
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. Nasopharyngeal carcinoma (NPC) lacks effective diagnostic and therapeutic strategies, in particular at advanced stages. Here, the authors show that expression of the somatostatin receptor 2 is induced by Epstein-Barr virus in NPC and has a key role in the diagnosis, imaging, targeted therapies and prognosis of NPC.
登录
查看更多内容
影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
3.8
作者：
Dodd, Lori E.;Sengupta, Srikumar;Hildesheim, Allan
通讯作者：
Hildesheim, Allan
DOI：
10.1002/hed.23716
发表时间：
2015-08-01
影响因子：
2.9
作者：
Noorlag, Rob;van der Groep, Petra;van Es, Robert J. J.
通讯作者：
van Es, Robert J. J.
DOI：
10.1002/path.5130
发表时间：
2018-10
期刊：
The Journal of pathology
影响因子：
--
作者：
Lo AK;Lung RW;Dawson CW;Young LS;Ko CW;Yeung WW;Kang W;To KF;Lo KW
通讯作者：
Lo KW
影响因子：
7.3
作者：
Chung, Grace Tin-Yun;Lou, Wilson Pak-Kin;Lo, Kwok-Wai
通讯作者：
Lo, Kwok-Wai