Somatostatin analogues in the control of neuroendocrine tumours: efficacy and mechanisms

Abstract

Neuroendocrine tumours (NETs) represent a heterogeneous family of neoplasms, which may develop from different endocrine glands (such as the pituitary, the parathyroid or the neuroendocrine adrenal glands), endocrine islets (within the thyroid or pancreas) as well as from endocrine cells dispersed between exocrine cells throughout the digestive and respiratory tracts. The development of somatostatin analogues (SSA) as important diagnostic and treatment tools has revolutionised the clinical management of patients with NETs. However, although symptomatic relief and stabilisation of tumour growth for various periods of time are observed in many patients treated with SSA, tumour regression is rare. Possible mechanisms when this does occur include antagonism of local growth factor release and effects, probably including activation of tyrosine and serine-threonine phosphatases, and indirect effects via anti-angiogenesis. The development of new SSA, new drug combination therapies and chimaeric molecules should further improve the clinical management of these patients, as should a more complete understanding of their mode of action.

SSTR3 is a putative target for the medical treatment of gonadotroph adenomas of the pituitary

“…The SSAs octreotide and lanreotide bind mainly to SSTR2 and to a lesser extent to SSTR3 and SSTR5, and represent the mainstay of medical therapy of functioning somatotroph and thyrotroph adenomas (Ben-Shlomo & Melmed 2008, Grozinsky-Glasberg et al 2008, Theodoropoulou & Stalla 2013. Treatment of acromegalic patients with these SSAs reduces or normalizes growth hormone and insulin-like growth factor 1 levels and induces tumor shrinkage (Theodoropoulou & Stalla 2013).…”

Insulinoma: Literature’s Review (2)

“…However, grade 3/4 adverse events only occurred in approximately 5% of patients and therefore everolimus should be considered a safe and well tolerated treatment in patients with neuroendocrine tumors (abstract presented at ESMO 2010). An additional advantage of everolimus in the treatment of patients with metastatic insulinomas is its capability to increase blood glucose levels [78][79][80][81][82][83][84].…”

Neuroendocrine Tumors of the Lung

“…In contrast to well-differentiated neuroendocrine tumors, undifferentiated ones express SSTR (mainly SSTR 2 subtype) less frequently (and in lower density) [21]. SST may bind to five different subtypes of specific SST receptors located on the cell surface (SSTR 1 , SSTR 2 , SSTR 3 , SSTR 4 and SSTR 5 ) and acts as an important regulator of endocrine function by inhibiting the secretion of various hormones [20]. Synthetic analogues bind mainly to SSTR 2 , and much less to SSTR 5 .…”

“…Bronchial carcinoid tumors as well as high-grade NE neoplasms are staged by the same criteria as applied to NSCLC (7th edition of the TNM staging system) [20]. For patients with small cell carcinomas who have received neoadjuvant chemotherapy and/or radiation therapy, the quantification of therapy-induced tumor regression provides prognostic relevant information on tumor response and is defined according to Junker and Müller [29][30][31][32]: The regression grading (Bochumer Modell) based on resections of treated small cell carcinomas [29,30].…”