Agonists, Antagonists and Receptors of Somatostatin: Pathophysiological and Therapeutical Implications in Neoplasias
Abstract
:1. Introduction
2. Description of Somatostatin Receptors
2.1. Overview of Somatostatin Receptors
2.2. Structure and Properties of Somatostatin Receptors
2.3. Localization, Functions and Signaling Pathways of Somatostatin Receptors
2.3.1. SSTR1
2.3.2. SSTR2
2.3.3. SSTR3
2.3.4. SSTR4
2.3.5. SSTR5
2.4. Importance of Somatostatin Receptors in Tumoral Pathology
2.4.1. Somatostatin Receptors and Neuroendocrine Tumors
2.4.2. Somatostatin Receptors and Squamous Cell Carcinomas
2.4.3. Somatostatin Receptors and Reproductive System Carcinomas
2.4.4. Somatostatin Receptors and Digestive Carcinomas
3. Therapeutical Uses of Somatostatin Analogs in Neoplasias
Somatostatin Analog | Octreotide | Lanreotide | Pasireotide |
---|---|---|---|
Most effective administration route | Subcutaneous | Subcutaneous | Subcutaneous |
Cmax attainment | 30 min (subcutaneous) 1.67–2.5 h (oral) | n/a | 0.25–0.5 h |
Volume of distribution (VL) | 13.6–30.4 L | 15.1 L | >100 L |
Protein binding | 65% | n/a | 88% |
Metabolism | Liver | Gastrointestinal tract | Liver |
Half-life | 2.3–2.7 h | 22 d | 12 h |
Clearance | 7–10 L/h | 23.1 L/h | 7.6 L/h |
Elimination | Urinary (32%) Faecal (30–40%) | Urinary (<5%) Faecal (<0.5%) | Hepatic (48.3%) Urinary (7.63%) |
Somatostatin Analog | Condition | Tumor-Expressed SSTRs | References |
---|---|---|---|
Octreotide | Acromegaly | SSTR2, SSTR5 (minor role) | [269,270] |
Congenital hyperinsulinism | SSTR2 | [271] | |
Thymic tumors | SSTR2 (minor role), SSTR3 | [178] | |
Lymphoma (potential treatment) | SSTR2 | [272] | |
Neuroendrocrine tumors | SSTR2, SSTR5 (minor role) | [273] | |
Merkel cell carcinoma | SSTR2, SSTR5 | [274,275] | |
Hepatocellular carcinoma | All SSTRs | [21] | |
Lanreotide | Acromegaly | SSTR2 | [34] |
Neuroendocrine tumors | SSTR2, SSTR5 (minor role) | [273,276,277] | |
Hepatocellular carcinoma | All SSTRs | [278] | |
Pasireotide | Acromegaly | SSTR2 (minor role), SSTR5 | [34,279] |
Congenital hyperinsulinism (proposed) and drug-induce hyperglycaemia in Cushings syndrome | SSTR5 | [271,280] | |
Neuroendrocrine tumors | SSTR1, SSTR2, SSTR3, SSTR5 | [281] |
3.1. Therapeutical Uses of Octreotide in Neoplasias
3.1.1. Octreotide in the Treatment of Thymic Tumors
3.1.2. Octreotide in the Management and Treatment of Neuroendocrine Tumors (NETs)
3.1.3. Octreotide in the Treatment of Lymphomas
3.1.4. Octreotide in the Treatment of Merkel Cell Carcinoma
3.1.5. Octreotide in the Treatment of Hepatocellular Carcinoma (HCC)
3.2. Therapeutical Uses of Lanreotide in Neoplasias
3.3. Therapeutical Uses of Pasireotide in Neoplasias
4. Somatostatin Antagonists: Current Evidence and Studies
5. Discussion
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Receptor | First Cloning | MR * | Length | Chromosomal Location | Major Tissue Sites | References |
---|---|---|---|---|---|---|
SSTR1 | 1992 | 45,000 | 391 | 14q13 | Brain/CNS, gastrointestinal tract, pancreas | [27,28,29,30,31] |
SSTR2 | 1992 | 41,305 | 369 | 17q24 | Brain/CNS, gastrointestinal tract, pancreas, lymph tissue, adrenal glands | [27,32,33,34] |
SSTR3 | 1992 | 46,000 | 418 | 22q13.1 | Brain/CNS, pancreas, gastrointestinal tract, lymph tissue, adrenal glands | [35,36] |
SSTR4 | 1993 | 45,000 | 388 | 20p11.2 | Brain/CNS, retina, placenta | [32,37,38,39,40] |
SSTR5 | 1994 | 39,000 | 364 | 16p13.3 | Brain/CNS, pancreas, gastrointestinal tract, lymph tissue, adrenal glands, aortic smooth muscle cells, Sertoli cells | [5,41,42,43,44] |
SSTR | Functions | References |
---|---|---|
SSTR1 | Inhibition of GH, prolactin and calcitonin secretion, (possible) anti-inflammatory and anti-nociceptive, regulation of hippocampal function | [5,20,45] |
SSTR2 | Inhibition of gastrin, histamine, growth hormone, adrenocorticotropin, glucagon, insulin, TSH, interferon-γ secretion, modulation of eating and drinking behavior, inhibition of stress responses, antidepressant effects, retinal neuroprotection | [20,46,47,48,49,50,51,52] |
SSTR3 | Cell proliferation reduction and apoptosis induction, insulin release inhibition, growth hormone release inhibition | [20,53,54,55,56] |
SSTR4 | Learning and memory, locomotor activity increase, possible modulation of behavioral responses | [5,20,57,58] |
SSTR5 | Inhibition of growth hormone, adrenocorticotropin, insulin, glucagon-like peptide-1 and amylase secretion, (possible) anti-stress function, (possible) gastric emptying mediation | [5,20,59,60] |
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Periferakis, A.; Tsigas, G.; Periferakis, A.-T.; Tone, C.M.; Hemes, D.A.; Periferakis, K.; Troumpata, L.; Badarau, I.A.; Scheau, C.; Caruntu, A.; et al. Agonists, Antagonists and Receptors of Somatostatin: Pathophysiological and Therapeutical Implications in Neoplasias. Curr. Issues Mol. Biol. 2024, 46, 9721-9759. https://doi.org/10.3390/cimb46090578
Periferakis A, Tsigas G, Periferakis A-T, Tone CM, Hemes DA, Periferakis K, Troumpata L, Badarau IA, Scheau C, Caruntu A, et al. Agonists, Antagonists and Receptors of Somatostatin: Pathophysiological and Therapeutical Implications in Neoplasias. Current Issues in Molecular Biology. 2024; 46(9):9721-9759. https://doi.org/10.3390/cimb46090578
Chicago/Turabian StylePeriferakis, Argyrios, Georgios Tsigas, Aristodemos-Theodoros Periferakis, Carla Mihaela Tone, Daria Alexandra Hemes, Konstantinos Periferakis, Lamprini Troumpata, Ioana Anca Badarau, Cristian Scheau, Ana Caruntu, and et al. 2024. "Agonists, Antagonists and Receptors of Somatostatin: Pathophysiological and Therapeutical Implications in Neoplasias" Current Issues in Molecular Biology 46, no. 9: 9721-9759. https://doi.org/10.3390/cimb46090578