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 (SSTR2) expression in multiple clinical cohorts compris...
| Váldodahkkit: | , , , , , , , , |
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| Materiálatiipa: | Journal article |
| Giella: | English |
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Nature Research
2021
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| _version_ | 1826291996538437632 |
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| author | Lechner, M Schartinger, VH Steele, C Philpott, M Nibhani, R Koller, J Wells, G Oppermann, U Et al. |
| author_facet | Lechner, M Schartinger, VH Steele, C Philpott, M Nibhani, R Koller, J Wells, G Oppermann, U Et al. |
| author_sort | Lechner, M |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T03:07:54Z |
| format | Journal article |
| id | oxford-uuid:b32f52fc-2370-4fd0-b5e8-1c6c196bafbc |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:07:54Z |
| publishDate | 2021 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:b32f52fc-2370-4fd0-b5e8-1c6c196bafbc2022-03-27T04:17:18ZSomatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b32f52fc-2370-4fd0-b5e8-1c6c196bafbcEnglishSymplectic ElementsNature Research2021Lechner, MSchartinger, VHSteele, CPhilpott, MNibhani, RKoller, JWells, GOppermann, UEt al.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. |
| spellingShingle | Lechner, M Schartinger, VH Steele, C Philpott, M Nibhani, R Koller, J Wells, G Oppermann, U Et al. Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy |
| title | Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy |
| title_full | Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy |
| title_fullStr | Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy |
| title_full_unstemmed | Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy |
| title_short | Somatostatin receptor 2 expression in nasopharyngeal cancer is induced by Epstein Barr virus infection: impact on prognosis, imaging and therapy |
| title_sort | somatostatin receptor 2 expression in nasopharyngeal cancer is induced by epstein barr virus infection impact on prognosis imaging and therapy |
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