SSTR2-targeting therapy in EBV-positive and EBV-negative metastatic nasopharyngeal carcinoma

Published on Friday, 24 April 2026

Abstract

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV) - associated malignancy prevalent in South Asia, and somatostatin receptors (SSTRs), particularly SSTR2, are expressed in NPC and other solid tumors, suggesting a potential therapeutic target.

We observed abundant SSTR2 expression in NPC cell lines and patient-derived xenografts (PDXs).

In the EBV-negative PDX-Li41 model, treatment with the SSTR2 agonist octreotide (OCT) significantly inhibited xenograft growth and showed additive effects with chemotherapy; transcriptomic and protein analyses revealed heterogeneous regulation of cell-cycle-related genes, upregulation of DNA replication pathways, downregulation of cell-signaling and neurotransmitter-release pathways, and reduced expression of CDK6, NF-κB, E2F1, CDK2, and BIRC5. In contrast, OCT did not suppress tumor growth in the EBV-positive PDX-B13 model, prompting the development of an octreotide-monomethyl auristatin E (OCT-MMAE) peptide-drug conjugate, which demonstrated efficient cellular internalization, a low IC50 (≈ 10-7 M), and significant inhibition of xenograft growth in both EBV-positive and EBV-negative PDX models.

Evaluation of 118 metastatic NPC tumors showed that 91.5% were SSTR2-positive, and high SSTR2 expression was associated with significantly shorter overall survival (P = 0.001768), indicating that SSTR2 is widely expressed, linked to poor prognosis, and represents a promising therapeutic target in NPC.

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About this publication.

The Di Bella's Method: Use of Somatostatin/Octreotide analogues and/or derivatives (since 1977), Melatonin (since 1974), Retinoids (40mg per day Beta-Carotene, 10mg per day ATRA and 10mg per day Axerophthol palmitate), Vitamin D, prolactin inhibitors Cabergoline and/or Bromocriptine with pseudo-Metronomic Chemotherapy Cyclophosphamide and/or Hydroxyurea (together with others chemical compounds) in Head&Neck Cancer (the dosage and administration schedule must be individualised for each patient):

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives since 1977);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);

- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);

- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);

- Prolactin inhibitors in oncology - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

The Di Bella's Method: Use Somatostatin/Octreotide analogues and/or derivatives since 1977 with Cabergoline and/or Bromocriptine associated with pseudo-Metronomic Chemotherapy Cyclophosphamide and/or Hydroxyurea - together with others chemical compounds - in several Oncological Pathologies:

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

- Pleural Mesothelioma: clinical records on 11 patients treated with Di Bella's Method;

- Malignant pleural mesothelioma, stage T3-T4. Consideration of a case study;

- Excellent result in a Mesothelioma case treated exclusively with Di Bella Method for over 4 years and still treatment with positive results;

- A case of advanced Multiple Myeloma treated with Di Bella Method (DBM) into total remission for 13 years;

- Neuroblastoma: Complete objective response to biological treatment;

- Cyclophosphamide plus Somatostatin, Bromocriptin, Retinoids, Melatonin and ACTH in the Treatment of Low-grade Non-Hodgkin’s Lymphomas at Advanced Stage: Results of a Phase II Trial;

- Relapse of High-Grade Non-Hodgkin’s Lymphoma After Autologous Stem Cell Transplantation: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Melatonin, Retinoids, and ACTH;

- Low-grade Non-Hodgkin Lymphoma at Advanced Stage: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Retinoids, and Melatonin;