Somatostatin Analogs Therapy in Gastroenteropancreatic Neuroendocrine Tumors: Current Aspects and New Perspectives

Abstract

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare tumors that present many clinical features secreting peptides and neuroamines that cause distinct clinical syndromes such as carcinoid syndrome. However most of them are clinically silent until late presentation with mass effects. Surgical resection is the first line treatment for a patient with a GEP-NET while in metastatic disease multiple therapeutic approaches are possible. GEP-NETs are able to express somatostatin receptors (SSTRs) bounded by somatostatin (SST) or its synthetic analogs, although the subtypes and number of SSTRs expressed are very variable. In particular, SST analogs are used frequently to control hormone-related symptoms while their anti-neoplastic activity seems to result prevalently in tumor stabilization. Patients who fail to respond or cease to respond to standard SST analogs treatment seem to have a response to higher doses of these drugs. For this reason, the use of higher doses of SST analogs will probably improve the clinical management of these patients.

AAVP displaying octreotide for ligand-directed therapeutic transgene delivery in neuroendocrine tumors of the pancreas

“…This tumor cell-specific ligand-receptor approach could address currently unmet needs (38)(39)(40) in patients with unresectable, inoperable, or metastatic pancreatic NETs. Indeed, we have shown that Oct-AAVP-TNF reduced tumor size, metabolic activity, and hormone secretion, and also increased survival in the Men1 transgenic mouse model, which faithfully recapitulates human disease with respect to both progression and response to therapy (29,30).…”

99mTc-EDDA/HYNIC-TOC in management of patients with head and neck somatostatin receptor positive tumors

“…No difference between imaging modalities ( 99m Tc EDDA/HYNIC-TOC vs. 18 F-FDG PET/CT or MRI) was noted. In group of NEC distant metastasis were found in 60% of the patients (3/5).…”

“…Patients using SSA showed symptomatic and biochemical improvement. SSA anti-tumor effects are still under investigation, they have direct impact on proliferative signaling pathways, on activation of apoptosis, on angiogenesis and on tumor stabilization [17,18].…”

Molecular challenges of neuroendocrine tumors (Review)

“…The expression of five subtypes of G-protein-coupled transmembrane somatostatin receptors (SSTRs) is very characteristic feature for NETs (54). Octreotide and lanreotide are somatostatin analogs proved to be useful in alleviation of of flushing and diarrhea which are associated with NETs secretion (55,56). The antitumor effect of somatostatin analogs has been established in many clinical trials (57)(58)(59).…”