Home > News > Antitumour Effects of Somatostatin Analogues in the Treatment of Neuroendocrine Tumours
Endocrine Oncology
Read Time: 2 mins

Antitumour Effects of Somatostatin Analogues in the Treatment of Neuroendocrine Tumours

Published Online: September 12th 2012 European Endocrinology, 2012;8(2):94-98 DOI: http://doi.org/10.17925/EE.2012.08.02.94
Authors: Diogo Assed Bastos, Brenda Gumz, Frederico Costa
Quick Links:
Abstract
Article
Article Information
Abstract:
Overview

Neuroendocrine tumours (NETs) are rare and heterogeneous neoplasms that can present with functional syndromes due to the hypersecretion of peptides. Somatostatin analogues (SSAs) have been used since the 1980s for the treatment of neuroendocrine tumours, with the aim of controlling the symptoms of functioning tumours and improving patients’ quality of life. Data from preclinical studies offer evidence of both direct and indirect mechanisms by which SSAs can exert antitumour effects. The activation of somatostatin receptors by SSAs leads to the activation of phosphotyrosine phosphatases, which control downstream apoptotic and antiproliferation signalling pathways. Also, the suppression of secretion of several growth factors and inhibition of antiangiogenic activity by SSAs indirectly inhibits tumour cell proliferation in vitro. Previous uncontrolled studies had shown tumour shrinkage and disappearance in response to the SSA octreotide. Recent results from the randomised and placebo-controlled PROMID trial have demonstrated that octreotide has antitumour activity in patients with metastatic mid-gut NETs. This article examines recent data providing evidence of the antitumour activity of somatostatin analogues.

Keywords

Neuroendocrine tumour (NET), somatostatin, antiproliferative activity, octreotide long-acting release (LAR), lanreotide

Article:

Neuroendocrine tumours (NETs) are rare neoplasms that arise from neuroendocrine cells which are present throughout the body.

Neuroendocrine tumours (NETs) are rare neoplasms that arise from neuroendocrine cells which are present throughout the body. NETs may be classified as functioning or non-functioning and are further differentiated based on the site of primary origin, histologic grade (low, intermediate or high) and proliferation rate.1 Functioning NETs are characterised by excessive hormone production and release, and cause hormonal syndromes (outlined in Table 1), while non-functioning NETs are not associated with a distinct hormonal syndrome – although they can secrete hormones and peptides at subclinical levels. Approximately 60–70 % of NET patients are diagnosed with disseminated metastatic disease.2 Even though many patients have indolent disease, some patients present with overtly aggressive tumours. Due to this heterogeneity, treatment is often individualised and may involve several modalities, such as cytoreductive surgery, non-surgical liver-directed therapies, somatostatin analogues, chemotherapy and, more recently, targeted agents.3 These treatments are used with two major objectives: to control the symptoms of hormone hypersecretion and to control tumour growth. The aim of this article is to review the antitumour effects of somatostatin (STS) analogues in the treatment of NETs.

Somatostatin
STS is a peptide produced by intestinal paracrine cells and plays a major role in inhibition of gastrointestinal (GI) endocrine secretion.4,5 STS acts as a paracrine, autocrine or neuronal regulatory molecule to inhibit glandular secretion, neurotransmission, smooth muscle contractility and absorption of nutrients, regulating the functioning of activated immune cells.5–7 STS exerts control over several neurophysiological functions, and is a pan-inhibitory agent for all known GI tract hormones.8 In the GI tract, STS promotes reduction of liver and splanchnic blood flow, inhibits GI and pancreatic secretions, inhibits gallbladder contractility and bile flow, slows GI transit, inhibits absorption of glucose and amino acids and inhibits tissue growth and proliferation.5

STS is a cyclic peptide. Its two biological molecular forms are somatostatin-14 (S-14) and somatostatin-28 (S-28), which are both expressed throughout the GI tract. STS is synthesised as part of a large precursor molecule that is cleaved, enzymatically processed and released by endocrine and nerve cells.9 STS binds to five different STS receptor subtypes (numbered 1–5) present at the surface of different endocrine cell types.

To view the full article in PDF or eBook formats, please click on the icons above.

Article Information:
Disclosure

The authors have no conflicts of interest to declare.

Correspondence

Frederico Costa, Oncology Center, Hospital Sírio-Libanês, Adma Jafet Street, 91, São Paulo, SP, 0138-050, Brazil. E: Frederico.costa@hsl.org.br

Support

The publication of this article was funded by Novartis. The views and opinions expressed are those of the authors and not necessarily those of Novartis.

Received

2012-06-26T00:00:00

References

  1. Oberg K, Castellano D, Current knowledge on diagnosis and staging of neuroendocrine tumors, Cancer Metastasis Rev, 2011;30(Suppl. 1):3–7.
  2. Modlin IM, Oberg K, Chung DC, et al., Gastroenteropancreatic neuroendocrine tumours, Lancet Oncol, 2008;9:61–72.
  3. Oberg KE, The management of neuroendocrine tumours: current and future medical therapy options, Clin Oncol (R Coll Radiol), 2012;24:282–93.
  4. Brazeau P, Vale W, Burgus R, et al., Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone, Science, 1973;179:77-9.
  5. Lamberts SW, van der Lely AJ, de Herder WW, Hofland LJ, Octreotide, N Engl J Med, 1996;334:246–54.
  6. Reichlin S, Somatostatin, N Engl J Med, 1983;309:1495–501.
  7. Reichlin S, Neuroendocrine-immune interactions, N Engl J Med, 1993;329:1246–53.
  8. Reichlin S, Secretion of somatostatin and its physiologic function, J Lab Clin Med, 1987;109:320–6.
  9. Patel YC, Somatostatin and its receptor family, Front Neuroendocrinol, 1999;20:157–98.
  10. Appetecchia M, Baldelli R, Somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine tumours, current aspects and new perspectives, J Exp Clin Cancer Res, 2010;29:19.
  11. Oberg K, Management of neuroendocrine tumours, Ann Oncol, 2004;15(Suppl. 4):iv293–8.
  12. Kvols LK, Moertel CG, O’Connell MJ, et al., Treatment of the malignant carcinoid syndrome. Evaluation of a long-acting somatostatin analogue, N Engl J Med, 1986;315:663–6.

Further Resources

Share this Article
Related Content In Endocrine Oncology
  • Copied to clipboard!
    accredited arrow-down-editablearrow-downarrow_leftarrow-right-bluearrow-right-dark-bluearrow-right-greenarrow-right-greyarrow-right-orangearrow-right-whitearrow-right-bluearrow-up-orangeavatarcalendarchevron-down consultant-pathologist-nurseconsultant-pathologistcrosscrossdownloademailexclaimationfeedbackfiltergraph-arrowinterviewslinkmdt_iconmenumore_dots nurse-consultantpadlock patient-advocate-pathologistpatient-consultantpatientperson pharmacist-nurseplay_buttonplay-colour-tmcplay-colourAsset 1podcastprinter scenerysearch share single-doctor social_facebooksocial_googleplussocial_instagramsocial_linkedin_altsocial_linkedin_altsocial_pinterestlogo-twitter-glyph-32social_youtubeshape-star (1)tick-bluetick-orangetick-red tick-whiteticktimetranscriptup-arrowwebinar Department Location NEW TMM Corporate Services Icons-07NEW TMM Corporate Services Icons-08NEW TMM Corporate Services Icons-09NEW TMM Corporate Services Icons-10NEW TMM Corporate Services Icons-11NEW TMM Corporate Services Icons-12Salary £ TMM-Corp-Site-Icons-01TMM-Corp-Site-Icons-02TMM-Corp-Site-Icons-03TMM-Corp-Site-Icons-04TMM-Corp-Site-Icons-05TMM-Corp-Site-Icons-06TMM-Corp-Site-Icons-07TMM-Corp-Site-Icons-08TMM-Corp-Site-Icons-09TMM-Corp-Site-Icons-10TMM-Corp-Site-Icons-11TMM-Corp-Site-Icons-12TMM-Corp-Site-Icons-13TMM-Corp-Site-Icons-14TMM-Corp-Site-Icons-15TMM-Corp-Site-Icons-16TMM-Corp-Site-Icons-17TMM-Corp-Site-Icons-18TMM-Corp-Site-Icons-19TMM-Corp-Site-Icons-20TMM-Corp-Site-Icons-21TMM-Corp-Site-Icons-22TMM-Corp-Site-Icons-23TMM-Corp-Site-Icons-24TMM-Corp-Site-Icons-25TMM-Corp-Site-Icons-26TMM-Corp-Site-Icons-27TMM-Corp-Site-Icons-28TMM-Corp-Site-Icons-29TMM-Corp-Site-Icons-30TMM-Corp-Site-Icons-31TMM-Corp-Site-Icons-32TMM-Corp-Site-Icons-33TMM-Corp-Site-Icons-34TMM-Corp-Site-Icons-35TMM-Corp-Site-Icons-36TMM-Corp-Site-Icons-37TMM-Corp-Site-Icons-38TMM-Corp-Site-Icons-39TMM-Corp-Site-Icons-40TMM-Corp-Site-Icons-41TMM-Corp-Site-Icons-42TMM-Corp-Site-Icons-43TMM-Corp-Site-Icons-44TMM-Corp-Site-Icons-45TMM-Corp-Site-Icons-46TMM-Corp-Site-Icons-47TMM-Corp-Site-Icons-48TMM-Corp-Site-Icons-49TMM-Corp-Site-Icons-50TMM-Corp-Site-Icons-51TMM-Corp-Site-Icons-52TMM-Corp-Site-Icons-53TMM-Corp-Site-Icons-54TMM-Corp-Site-Icons-55TMM-Corp-Site-Icons-56TMM-Corp-Site-Icons-57TMM-Corp-Site-Icons-58TMM-Corp-Site-Icons-59TMM-Corp-Site-Icons-60TMM-Corp-Site-Icons-61TMM-Corp-Site-Icons-62TMM-Corp-Site-Icons-63TMM-Corp-Site-Icons-64TMM-Corp-Site-Icons-65TMM-Corp-Site-Icons-66TMM-Corp-Site-Icons-67TMM-Corp-Site-Icons-68TMM-Corp-Site-Icons-69TMM-Corp-Site-Icons-70TMM-Corp-Site-Icons-71TMM-Corp-Site-Icons-72