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entities are further summarized into 2 groups based relieving symptoms and, in recent years, of suppressing
on their grade of biological aggressiveness: well- tumor growth and spread is a necessary option for
differentiated neoplasms including typical and atypical advanced NETs that are unsuitable for surgery. [14]
carcinoids, and poorly differentiated ones involving
LCNEC and SCLC. Among medical therapies, Short synthetic analogues
of somatostatin (SSAs) represent one of the possible
Despite comprehensive and notable medical progress, options in the presence of carcinoid syndrome. SSAs
therapeutic options are still inadequate for gastrointestinal include octreotide, lanreotide, vapreotide, seglitide,
and bronchopulmonary (BP) neuroendocrine tumors, and pasireotide. SSAs’ affinity for the distinct receptor
due to the lack of in-depth knowledge of molecular subtypes is different than that of native somatostatin. [15-17]
mechanisms and predictive factors. This review aims Five different somatostatin receptor (SSTR) subtypes have
to summarize the current knowledge about pathways been characterized in humans (SSTR1-SSTR5) [Figure 1].
involved in advanced, sporadic well- and moderately [18-22] SSTR2 represents the principal target for octreotide,
differentiated GEP-NETs and in BP carcinoids, lanreotide, vapreotide, seglitide, and pasireotide.
highlighting available evidences on biological and Furthermore, pasireotide shows a higher binding capacity
targeted therapies. towards SSTR1, activating also SSTR 3 and 5. [23-25] For
this reason, different SSAs show a distinct affinity with
SHORT SYNTHETIC ANALOGUES OF their own ligands, eliciting various biological and clinical
SOMATOSTATIN activities in the same cell type through the activation
[16]
of subsets of disparate intracellular mediators. [23,24,26]
The primary treatment objective for patients with NETs Nevertheless, the natural ligands of SSTR1-5 can bind all
is cure. Symptom control and limitation of disease somatostatin receptors with high affinity.
progression represent the secondary goals. The traditional
first and only possible radical approach is surgery. SSTRs were expressed in over 80% of well-differentiated
However, NETs are frequently diagnosed in advanced GEP-NENs. SSTR in particular has been observed to
stages when curative surgery is generally not possible. predominate in both gastrointestinal-NENs (90%) and
Medical management with the principal objective of primitive-NETs (P-NETs), especially in gastrinomas,

Figure 1: Principal pathways involved in carcinogenesis and progression of NENs. EGFR: epidermal growth factor receptor; VEGFR2: vascular endothelial
growth factor receptor 2; IGF1R: insulin-like growth factor 1 receptor; SSTR: somatostatin receptors; SOS: save our souls; PI3K: phosphoinositide 3-kinase;
PIP2: phosphatidylinosital biphosphate 2; PIP3: phosphatidylinosital biphosphate 3; PTEN: phosphatase and tensin homolog; MEK: methyl ethyl ketone;
ERK: extracellular signal-regulated kinase ; AKT: protein kinase B; mTOR: mammalian target of rapamycin; MAPK: mitogen-activated protein kinase
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Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ August 31, 2016 ¦