Somatostatin receptors: from signaling to clinical practice

Front Neuroendocrinol. 2013 Aug;34(3):228-52. doi: 10.1016/j.yfrne.2013.07.005. Epub 2013 Jul 18.


Somatostatin is a peptide with a potent and broad antisecretory action, which makes it an invaluable drug target for the pharmacological management of pituitary adenomas and neuroendocrine tumors. Somatostatin receptors (SSTR1, 2A and B, 3, 4 and 5) belong to the G protein coupled receptor family and have a wide expression pattern in both normal tissues and solid tumors. Investigating the function of each SSTR in several tumor types has provided a wealth of information about the common but also distinct signaling cascades that suppress tumor cell proliferation, survival and angiogenesis. This provided the rationale for developing multireceptor-targeted somatostatin analogs and combination therapies with signaling-targeted agents such as inhibitors of the mammalian (or mechanistic) target of rapamycin (mTOR). The ability of SSTR to internalize and the development of rabiolabeled somatostatin analogs have improved the diagnosis and treatment of neuroendocrine tumors.

Keywords: 5-HIAA; 5-hydroxyindoleacetic acid; 70-kDa ribosomal protein S6 kinase; ACTH; AIP; AKT8 virus oncogene cellular homolog; Akt; B-cell lymphoma 2; BNCT; Bax; Bcl-2; Bcl-2-associated X; CCK; DAG; DOTA; DR4; DTPA; Dopastatin; GH; GI; GIP; GLP-1; GSK3β; Grb; Gsp; Gsα subunit protein; HGCT; IGF-1; IP3; IRS-1; JAK; JNK; Janus kinase; LAR; LDL; MAPK; Men1; NET; NHE1; NOS; Na(+)/H(+) exchanger; Neuroendocrine tumor; OGTT; Octreotide; PET; PFS; PI3K; PIP2; PKA/C; PLA/C; POMC; PRL; PTP; Pasireotide; Pituitary; Proliferation; RKIP; Raf; Raf kinase inhibitory protein; Ras; SH2; SH2-containing phosphatase; SHP; SPECT; SSTR; STAT3/5b; Signal transduction; Somatostatin; Somatostatin receptors; Sos; TNFR1; TPE; TSH; TTP; UFC; VEGF; Zac1; adrenocorticotropic hormone; aryl hydrocarbon receptor interacting protein; boron neutron capture therapy; c-Jun NH(2)-terminal kinase; cAMP/cGMP; cholecystokinin; cyclic adenosine/guanosine monophosphate; death receptor 4; diacylglycerol; diethylenetriaminepentaacetic acid; gastrointestinal; glucagon-like peptide 1; glucose-dependent insulinotropic polypeptide; glycogen synthase kinase 3β; growth factor receptor bound protein; growth hormone; hyperglycemic clamp test; inositol 1,4,5-trisphosphate; insulin receptor substrate 1; insulin-like growth factor 1; long-acting release (or repeatable); low-density lipoprotein; mTOR; mammalian (or mechanistic) target of rapamycin; mitogen-activated protein kinase; multiple endocrine neoplasia 1; neuroendocrine tumors; nitric oxide synthase (endothelial/neuronal); oral glucose tolerance test; p70/S6K; phosphatidylinositol 3-kinase; phosphatidylinositol 4,5-bisphosphate; phospholipase A/C; positron emission tomography; pro-opiomelanocortin; progression-free survival; prolactin; protein kinase A/C; protein tyrosine phosphatase; rapidly accelerated fibrosarcoma; rat sarcoma; rous sarcoma oncogene cellular homolog; signal transducer and activator of transcription 3/5b; single photon emission computed tomography; somatostatin receptor; son of sevenless; src; src homology 2; tetraazacyclododecanetetraacetic acid; thyroid-stimulating hormone; time to tumor progression; transient permeability enhancer; tumor necrosis factor receptor 1; urinary free cortisol; vascular endothelial growth factor; zinc finger protein that induces apoptosis and cell cycle arrest.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carcinoma, Neuroendocrine / diagnosis
  • Carcinoma, Neuroendocrine / drug therapy*
  • Cell Proliferation / drug effects
  • Dopamine / analogs & derivatives
  • Dopamine / therapeutic use
  • Humans
  • Octreotide / therapeutic use
  • Peptides, Cyclic / therapeutic use
  • Radiopharmaceuticals
  • Receptors, Somatostatin / drug effects*
  • Receptors, Somatostatin / physiology*
  • Signal Transduction / drug effects
  • Somatostatin / adverse effects
  • Somatostatin / analogs & derivatives
  • Somatostatin / therapeutic use
  • TOR Serine-Threonine Kinases / antagonists & inhibitors


  • PTR 3173
  • Peptides, Cyclic
  • Radiopharmaceuticals
  • Receptors, Somatostatin
  • SSTR2 protein, human
  • somatostatin receptor type 1
  • lanreotide
  • Somatostatin
  • pasireotide
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • TBR-760
  • Octreotide
  • Dopamine