Somatostatin analogues: multiple roles in cellular proliferation, neoplasia, and angiogenesis

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Published on Wednesday, 06 June 2018

Abstract

Angiogenesis, the development of new blood vessels is a crucial process both for tumor growth and metastatic dissemination. Additionally, dysregulation in angiogenesis has been implicated in the pathogenesis of cardiovascular disease, proliferative retinopathy, diabetic nephropathy, and rheumatoid arthritis (RA).

The neuropeptide somatostatin has been shown to be a powerful inhibitor of neovascularization in several experimental models. Furthermore, somatostatin receptors (sst) are expressed on endothelial cells; particularly, sst2 has been found to be uniquely up-regulated during the angiogenic switch, from quiescent to proliferative endothelium.

The present manuscript reviews the anti-angiogenic activity of somatostatin and its analogues in neoplastic and nonneoplastic disease. The role of sst subtypes particularly sst2 in mediating its angioinhibitory activity is described.

Somatostatin agonists may also exert their anti-angiogenic activity indirectly by inhibition of growth factors like vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis or through its immunomodulatory effects. However, the therapeutic utility of somatostatin agonists as anti-angiogenic drugs in these diseases remains confusing because of conflicting results from different studies.

More basic research, as well as patient-oriented studies, is required to firmly establish the clinical potential of somatostatin agonists in therapeutic angiogenesis. The currently available somatostatin agonists have high affinity of sst2 with lower affinities for sst3 and sst5.

The emergence of novel somatostatin agonists especially bispecific analogues (agonists targeting multiple cellular receptors) and conjugates (synthesized by chemically linking somatostatin analogues with other antineoplastic agents) with improved receptor specificity signify a new generation of anti-angiogenics, which may represent novel strategies in the treatment of neovascularization-related diseases.

 

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See also:

- Somatostatin in oncology, the overlooked evidences;

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

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

- Congenital fibrosarcoma in complete remission with Somatostatin, Retinoids, Vitamin D3, Vitamin E, Vitamin C, Melatonin, Calcium, Chondroitin sulfate associated with low doses of Cyclophosphamide in a 14-year Follow Up;

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature;

- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

- The Di Bella Method Increases by the 30% the survival rate for Pancreas tumors and for this reason should be proposed as first line therapy for this type of cancer;

- Oesophageal squamocellular carcinoma: a complete and objective response;

- Neuroblastoma: Complete objective response to biological treatment;

- 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;

- 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;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma.