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

Autor: Lechner M; UCL Cancer Institute, University College London, London, UK. m.lechner@ucl.ac.uk.; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, CA, USA. m.lechner@ucl.ac.uk.; Barts Health NHS Trust, London, UK. m.lechner@ucl.ac.uk.; Royal National Throat, Nose and Ear Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, UK. m.lechner@ucl.ac.uk., Schartinger VH; Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria., Steele CD; UCL Cancer Institute, University College London, London, UK., Nei WL; Divisions of Radiation Oncology and Medical Sciences, National Cancer Centre, Singapore, Singapore.; Oncology Academic Programme, Duke-NUS Medical School, Singapore, Singapore., Ooft ML; King´s College Hospitals, NHS Foundation Trust, London, UK.; Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands., Schreiber LM; Institute of Virology and Christian Doppler Laboratory for Viral Immunotherapy of Cancer, Medical University of Innsbruck, Innsbruck, Austria., Pipinikas CP; UCL Cancer Institute, University College London, London, UK., Chung GT; Department of Anatomical and Cellular Pathology and State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China., Chan YY; Department of Anatomical and Cellular Pathology and State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China., Wu F; Department of Anatomical and Cellular Pathology and State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China., To KF; Department of Anatomical and Cellular Pathology and State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China., Tsang CM; Department of Anatomical and Cellular Pathology and State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China., Pearce W; UCL Cancer Institute, University College London, London, UK., Morelli D; UCL Cancer Institute, University College London, London, UK., Philpott M; Botnar Research Centre, University of Oxford, Oxford, UK., Masterson L; Department of Otolaryngology, Addenbrooke's Hospital, Cambridge, UK., Nibhani R; Botnar Research Centre, University of Oxford, Oxford, UK., Wells G; Botnar Research Centre, University of Oxford, Oxford, UK., Bell CG; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK., Koller J; Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria.; Botnar Research Centre, University of Oxford, Oxford, UK., Delecluse S; German Cancer Research Centre (DKFZ) and Inserm, Unit F100/U1074, Heidelberg, Germany., Yip YL; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China., Liu J; UCL Cancer Institute, University College London, London, UK., Forde CT; Royal National Throat, Nose and Ear Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, UK., Forster MD; UCL Cancer Institute, University College London, London, UK.; Royal National Throat, Nose and Ear Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, UK., Jay A; Department of Histopathology, University College London Hospitals NHS Trust, Euston Road, London, UK., Dudás J; Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria., Krapp A; Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria., Wan S; Institute of Nuclear Medicine, University College Hospital, Euston Road, London, UK., Uprimny C; Department of Nuclear Medicine, Medical University of Innsbruck, Innsbruck, Austria., Sprung S; Department of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Innsbruck, Austria., Haybaeck J; Department of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Innsbruck, Austria.; Diagnostic & Research Center for Molecular Biomedicine, Institute of Pathology, Medical University of Graz, Graz, Austria., Fenton TR; School of Biosciences, University of Kent, Canterbury, UK., Chester K; UCL Cancer Institute, University College London, London, UK., Thirlwell C; UCL Cancer Institute, University College London, London, UK.; University of Exeter College of Medicine and Health, Exeter, UK., Royle G; UCL Cancer Institute, University College London, London, UK., Marafioti T; UCL Cancer Institute, University College London, London, UK., Gupta R; UCL Cancer Institute, University College London, London, UK., Indrasari SR; ENT Head and Neck Surgery Department, Universitas Gadjah Mada, Dr. Sardjito Hospital, Yogyakarta, Indonesia., Herdini C; ENT Head and Neck Surgery Department, Universitas Gadjah Mada, Dr. Sardjito Hospital, Yogyakarta, Indonesia., Slim MAM; Department of Ear, Nose and Throat, University Hospital Crosshouse, Crosshouse, Kilmarnock, UK., Indrawati I; Department of Anatomical Pathology, Universitas Gadjah Mada, Dr. Sardjito Hospital, Yogyakarta, Indonesia., Sutton L; Barts Health NHS Trust, London, UK., Fles R; Department of Head and Neck Surgery and Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands., Tan B; ENT Head and Neck Surgery Department, Universitas Gadjah Mada, Dr. Sardjito Hospital, Yogyakarta, Indonesia.; Department of ENT/Head and Neck Surgery, Maastricht University Medical Center (MUMC), Maastricht, The Netherlands., Yeong J; Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore.; Institute of Molecular and Cell Biology, A*STAR, Singapore, Singapore., Jain A; Division of Medical Oncology, National Cancer Centre, Singapore, Singapore., Han S; Division of Medical Oncology, National Cancer Centre, Singapore, Singapore., Wang H; Divisions of Radiation Oncology and Medical Sciences, National Cancer Centre, Singapore, Singapore., Loke KSH; Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital, Singapore, Singapore., He W; Department of Oncology, The Second Clinical Medical College, Shenzhen People's Hospital, Jinan University, Shenzhen, Guangdong, China., Xu R; Department of Oncology, The Second Clinical Medical College, Shenzhen People's Hospital, Jinan University, Shenzhen, Guangdong, China., Jin H; Department of Pathology, The Second Clinical Medical College, Shenzhen People's Hospital, Jinan University, Shenzhen, Guangdong, China., Cheng Z; Department of Pathology, The Second Clinical Medical College, Shenzhen People's Hospital, Jinan University, Shenzhen, Guangdong, China., Howard D; Royal National Throat, Nose and Ear Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, UK.; ENT Department, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK., Hwang PH; Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Palo Alto, CA, USA., Le QT; Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, CA, USA., Tay JK; Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, USA.; Department of Otolaryngology-Head and Neck Surgery, National University of Singapore, Singapore, Singapore., West RB; Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, USA., Tsao SW; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China., Meyer T; UCL Cancer Institute, University College London, London, UK., Riechelmann H; Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria., Oppermann U; Botnar Research Centre, University of Oxford, Oxford, UK.; Freiburg Institute for Advanced Studies (FRIAS), University of Freiburg, 79085, Freiburg, Germany., Delecluse HJ; German Cancer Research Centre (DKFZ) and Inserm, Unit F100/U1074, Heidelberg, Germany., Willems SM; Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.; Department of Pathology, University Medical Center Groningen, Groningen, The Netherlands., Chua MLK; Divisions of Radiation Oncology and Medical Sciences, National Cancer Centre, Singapore, Singapore.; Oncology Academic Programme, Duke-NUS Medical School, Singapore, Singapore., Busson P; CNRS-UMR 9018-METSY, Gustave Roussy and Université Paris-Saclay, Villejuif, France., Lo KW; Department of Anatomical and Cellular Pathology and State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China., Wollmann G; Institute of Virology and Christian Doppler Laboratory for Viral Immunotherapy of Cancer, Medical University of Innsbruck, Innsbruck, Austria., Pillay N; UCL Cancer Institute, University College London, London, UK.; Department of Cellular and Molecular Pathology, Royal National Orthopaedic Hospital NHS Trust, Stanmore, UK., Vanhaesebroeck B; UCL Cancer Institute, University College London, London, UK. bart.vanh@ucl.ac.uk., Lund VJ; UCL Cancer Institute, University College London, London, UK. v.lund@ucl.ac.uk.; Royal National Throat, Nose and Ear Hospital and Head and Neck Centre, University College London Hospitals NHS Trust, London, UK. v.lund@ucl.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Jan 05; Vol. 12 (1), pp. 117. Date of Electronic Publication: 2021 Jan 05.
DOI: 10.1038/s41467-020-20308-8
Abstrakt: 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 68 Ga-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.
Databáze: MEDLINE