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International Journal of Molecular... Dec 2023Somatostatin (SST), a growth hormone inhibitory peptide, is expressed in endocrine and non-endocrine tissues, immune cells and the central nervous system (CNS).... (Review)
Review
Somatostatin (SST), a growth hormone inhibitory peptide, is expressed in endocrine and non-endocrine tissues, immune cells and the central nervous system (CNS). Post-release from secretory or immune cells, the first most appreciated role that SST exhibits is the antiproliferative effect in target tissue that served as a potential therapeutic intervention in various tumours of different origins. The SST-mediated in vivo and/or in vitro antiproliferative effect in the tumour is considered direct via activation of five different somatostatin receptor subtypes (SSTR1-5), which are well expressed in most tumours and often more than one receptor in a single cell. Second, the indirect effect is associated with the regulation of growth factors. SSTR subtypes are crucial in tumour diagnosis and prognosis. In this review, with the recent development of new SST analogues and receptor-specific agonists with emerging functional consequences of signaling pathways are promising therapeutic avenues in tumours of different origins that are discussed.
Topics: Humans; Receptors, Somatostatin; Somatostatin; Growth Hormone; Neoplasms; Biology
PubMed: 38203605
DOI: 10.3390/ijms25010436 -
ESMO Open Aug 2020Neuroendocrine tumours (NETs) constitute a heterogeneous group of neoplasms characterised by variable endocrine activity and somatostatin receptor expression, with the... (Review)
Review
Neuroendocrine tumours (NETs) constitute a heterogeneous group of neoplasms characterised by variable endocrine activity and somatostatin receptor expression, with the latter allowing the use of targeted therapeutic concepts. Currently accepted treatment strategies for advanced well-differentiated NET include somatostatin analogues octreotide and lanreotide, peptide receptor radionuclide therapy using radiolabelled somatostatin analogues, mammalian target of Rapamycin inhibitor everolimus, tyrosine kinase inhibitor sunitinib, interferon alpha and classical cytostatic, such as streptozotocin-based and temozolomide-based treatment. Indication, use and approval of these treatments differ based on primary tumour origin, grading and symptomatic burden and require an optimised multidisciplinary cooperation of medical oncologists, endocrinologists and nuclear medicine specialists. Interestingly, hot topics in oncology including immunotherapy and use of next-generation-sequencing techniques currently play a minor role for the treatment of NETs. The recent revision of the WHO classification including the recognition of the novel NET G3 category allows for potentially more tailored treatment strategies in the near future. However, this new entity also poses a therapeutic challenge as only limited data are currently available. The present article aims to provide an overview on our personal treatment concepts for advanced NETs with a focus on tumours of gastroenteropancreatic origin.
Topics: Everolimus; Humans; Neuroendocrine Tumors; Octreotide; Receptors, Somatostatin; Sunitinib
PubMed: 32817134
DOI: 10.1136/esmoopen-2020-000811 -
Neuropeptides Dec 2019Itch is a somatosensory sensation that informs the organism about the presence of potentially harmful substances or parasites, and initiates scratching to remove the... (Review)
Review
Itch is a somatosensory sensation that informs the organism about the presence of potentially harmful substances or parasites, and initiates scratching to remove the threat. Itch-inducing (pruritogenic) substances activate primary afferent neurons in the skin through interactions with specific receptors that converts the stimulus into an electrical signal. These signals are conveyed to the dorsal horn of the spinal cord through the release of neurotransmitters such as natriuretic polypeptide b and somatostatin, leading to an integrated response within a complex spinal interneuronal network. A large sub-population of somatostatin-expressing spinal interneurons also carry the Neuropeptide Y (NPY) Y1 receptor, indicating that NPY and somatostatin partly regulate the same neuronal pathway. This review focuses on recent findings regarding the role of the NPY/Y1 and somatostatin/SST receptor in itch, and also presents data integrating the two neurotransmitter systems.
Topics: Animals; Humans; Neural Pathways; Neurons; Neuropeptide Y; Pruritus; Receptors, Neuropeptide Y; Receptors, Somatostatin; Somatostatin; Spinal Cord
PubMed: 31668651
DOI: 10.1016/j.npep.2019.101976 -
Journal of Nuclear Medicine : Official... Sep 2017Somatostatin receptor (sstr) scintigraphy for imaging and sstr analogs for treatment have been used for more than 20 y. An important improvement in recent years was the... (Review)
Review
Somatostatin receptor (sstr) scintigraphy for imaging and sstr analogs for treatment have been used for more than 20 y. An important improvement in recent years was the introduction of peptide receptor radionuclide therapy with radiolabeled sstr agonists, such as [Y-DOTA,Tyr]octreotide or [Lu-DOTA,Tyr]octreotide (Y- or Lu-DOTATOC, respectively) and [Lu-DOTA,Tyr]octreotate (Lu-DOTATATE). PET/CT with Ga-labeled sstr agonists, such as Ga-DOTATOC, Ga-DOTATATE, and [Ga-DOTA,1-Nal]octreotide (Ga-DOTANOC), plays an important role in staging and restaging neuroendocrine tumors. Most importantly, sstr scintigraphy and sstr PET/CT can distinguish patients who will qualify for and benefit from peptide receptor radionuclide therapy. This characteristic of sstr targeting is important because it allows a personalized treatment approach (theranostic approach). Until recently, it was thought that internalization of the radiolabeled agonist was mandatory for sstr-mediated imaging and therapy. It was Ginj et al. who proposed in 2006 the paradigm shift that radiolabeled sstr antagonists may perform better than agonists despite the lack of internalization. Despite the rather limited number of head-to-head comparisons of sstr antagonists and agonists, the superiority of sstr antagonists was demonstrated in several cases. From a small library of sstr antagonists, the analog JR11 (Cpa-c[d-Cys-Aph(Hor)-d-Aph(Cbm)-Lys-Thr-Cys]-d-Tyr-NH), an antagonist with selectivity for sstr subtype 2, showed the best overall characteristics for sstr subtype 2 targeting and was therefore selected for clinical translation. JR11 is under clinical development as a PET imaging agent when labeled with Ga (Ga-NODAGA-JR11 or Ga-OPS202) and as a therapeutic agent when labeled with Lu (Lu-DOTA-JR11 or Lu-OPS201). In this article, we discuss the development and current status of radiolabeled sstr antagonists. Evidence based on preclinical work, on quantitative in vivo autoradiography of human tumor slices, and on human data now supports a shift to sstr antagonists.
Topics: Animals; Diagnostic Imaging; Drug Discovery; Humans; Isotope Labeling; Molecular Targeted Therapy; Receptors, Somatostatin
PubMed: 28864614
DOI: 10.2967/jnumed.116.186783 -
Swiss Medical Weekly Feb 2019Molecular imaging has found numerous applications in oncology as many tumours express or activate tumour specific target molecules or pathways. This relatively new... (Review)
Review
Molecular imaging has found numerous applications in oncology as many tumours express or activate tumour specific target molecules or pathways. This relatively new imaging technique results in a better localisation of tumours and improved tumour staging, especially in the setting of hybrid imaging that is in combination with morphological imaging such as computed tomography. In well differentiated neuroendocrine tumours, somatostatin receptor imaging, as one of the first examples of receptor targeted imaging in humans, plays an important role in the diagnostic work-up of these patients. In poorly differentiated neuroendocrine tumours or medullary thyroid carcinoma, 18F-fluorodeoxyglucose PET/CT and dihydroxyphenylalanine PET/CT play an important role due to the limitations of the somatostatin receptor imaging in these tumour entities. These limitations prompted the development of innovations such as radiolabelled somatostatin receptor antagonists for imaging all types of NET and glucagon-like peptide-1 receptor agonists for the imaging of insulinomas. The current review summarises the actual state of knowledge in the field.
Topics: Carcinoma, Neuroendocrine; Fluorodeoxyglucose F18; Glucagon-Like Peptide-1 Receptor; Humans; Molecular Imaging; Neoplasm Staging; Neuroendocrine Tumors; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Receptors, Somatostatin; Thyroid Neoplasms; Tomography, X-Ray Computed
PubMed: 30852831
DOI: 10.4414/smw.2019.20017 -
Postepy Biochemii Oct 2018Somatostatin is a peptide that participates in numerous biochemical and signaling pathways. It functions via receptors (SSTRs1-5), which belong to the family of... (Review)
Review
Somatostatin is a peptide that participates in numerous biochemical and signaling pathways. It functions via receptors (SSTRs1-5), which belong to the family of receptors coupled with protein G. All somatostatin receptors are characterized by a certain degree of homology in molecular structure. The cell effects of their agonists in peripheral tissues rely mainly on the inhibition of the hormones release. Somatostatin is also an important neuromodulator and neurotransmitter. SSTRs may affect other receptors, forming structural and functional homodimers and heterodimers. SSTRs play also role in the regulation of physiological processes, such as itching and pain, reproductive functions, regulation of feeding or mood. Besides physiological functions, SSTRs contribute also to the pathogenesis of glial tumors, neurodegenerative diseases, or post hemorrhagic stroke changes. Recent years of research have provided new data regarding the role of somatostatin receptor signaling pathways in the brain and the knowledge in this field is developing rapidly.
Topics: Brain; Humans; Neurotransmitter Agents; Receptors, Somatostatin; Signal Transduction; Somatostatin
PubMed: 30656906
DOI: 10.18388/pb.2018_133 -
Nuclear Medicine Review. Central &... 2016Neuroendocrine neoplasms (NENs) show wide spectrum of clinical course - from benign biological potential to recurrences and rapidly progressive disease. Somatostatin... (Review)
Review
Neuroendocrine neoplasms (NENs) show wide spectrum of clinical course - from benign biological potential to recurrences and rapidly progressive disease. Somatostatin analogs that bind to somatostatin receptor are part of the therapy; detection and evaluation of activation of somatostatin receptor subtypes are part of the process of new therapy induction. When using RT-PCR method and immunohistochemistry, it is possible to detect more than two SSTR subtypes in majority or all neuroendo-crine neoplasms regardless tumor origin. Generally with some exceptions, from the viewpoint of tumor grade - apart the site of origin, there is a tendency to decrease the percentage of SSTRs expression; 100% (G1, 2)-85.7% (G3) for SSTR 1; 81.8% (G1, 2)-61.9% (G3) for SSTR 2; 54.5% (G1, 2)-52.4% (G3) for SSTR 3; 9% (G1, 2)-4.8% (G3) for SSTR 5. Different studies indi-cate significant differences in the expression of SSTR 1 and 2A and 2B between NEC G3 small cell type and non-small cell type. Further research on SSTRs expression in NEN could serve as base to development and improvement of somatostatin analogs' pharmacotherapy in patients with unsatisfactory course.
Topics: Gene Expression Regulation, Neoplastic; Humans; Neuroendocrine Tumors; Receptors, Somatostatin
PubMed: 27479788
DOI: 10.5603/NMR.2016.0022 -
Surgical Oncology Clinics of North... Oct 2022Positron emission tomography (PET) with somatostatin receptor (SSTR) ligands has taken the lead in the imaging of neuroendocrine tumors (NETs). In this article, we... (Review)
Review
Positron emission tomography (PET) with somatostatin receptor (SSTR) ligands has taken the lead in the imaging of neuroendocrine tumors (NETs). In this article, we review the role of SSTR PET scan in the management of NETs, including the indications for the scan, pitfalls in interpretation, and imaging selection criteria for peptide receptor radionuclide therapy. We also discuss the complementary role of fluorodeoxyglucose PET particularly for patients with high-grade disease.
Topics: Humans; Ligands; Neuroendocrine Tumors; Positron-Emission Tomography; Radioisotopes; Radiopharmaceuticals; Receptors, Somatostatin
PubMed: 36243499
DOI: 10.1016/j.soc.2022.06.009 -
Endocrine Practice : Official Journal... Mar 2022Acromegaly is associated with significant morbidity and mortality if it is not appropriately treated. In addition to insulin-like growth factor 1 and growth hormone... (Review)
Review
Acromegaly is associated with significant morbidity and mortality if it is not appropriately treated. In addition to insulin-like growth factor 1 and growth hormone normalization as well as tumor shrinkage, the treatment goals include relieving symptoms, managing complications, and improving patients' quality of life. Surgical resection is a first-line treatment option for most patients, with few being pretreated preoperatively with medications. Somatostatin receptor ligands (SRLs), injectable and, more recently, oral capsules, have been the cornerstone of first-line medical therapy for persistent disease. However, several factors, including sparsely granulated adenomas, absent or low somatostatin receptor status, T2-hyperintensity imaging, young age, and aryl hydrocarbon receptor-interacting protein mutations, can predict first-generation SRL resistance. Patients with these characteristics may be better candidates for the growth hormone receptor antagonist pegvisomant, or in cases of large tumors, the second-generation SRL pasireotide. Combination therapy should be further pursued in patients who remain biochemically uncontrolled or have a high remnant tumor after monotherapy. An efficacious and cost-effective pegvisomant dose-sparing effect of SRLs when used in combination has been demonstrated. With such a wide array of medical treatment options, it is becoming increasingly important to tailor treatment to patients' unique characteristics and preferences, with a goal of personalizing management to achieve high-quality outcomes.
Topics: Acromegaly; Adenoma; Combined Modality Therapy; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Quality of Life; Receptors, Somatostatin
PubMed: 35032649
DOI: 10.1016/j.eprac.2021.12.017 -
Current Oncology Reports Nov 2021Accurate imaging is crucial for correct diagnosis, staging, and therapy of neuroendocrine neoplasms (NENs). The search for the optimal imaging technique has triggered... (Review)
Review
PURPOSE OF REVIEW
Accurate imaging is crucial for correct diagnosis, staging, and therapy of neuroendocrine neoplasms (NENs). The search for the optimal imaging technique has triggered rapid development in the field. This review aims at giving an overview on contemporary imaging methods and providing an outlook on current progresses.
RECENT FINDINGS
The discovery of molecular targets due to the overexpression of specific peptide hormone receptors on the NEN's surface has triggered the development of multiple radionuclide imaging modalities. In addition to the established imaging technique of targeting somatostatin receptors, several alternative radioligands have been developed. Targeting the glucagon-like peptide-1 receptor by exendin-4 has a high sensitivity in localizing insulinomas. For dedifferentiated NENs, new molecular targets such as the C-X-C motif chemokine-receptor-4 have been evaluated. Other new targets involve the fibroblast activation protein and the cholecystokinin-2 receptors, where the ligand minigastrin opens new possibilities for the management of medullary thyroid carcinoma. Molecular imaging is an emerging field that improves the management of NENs.
Topics: Humans; Neuroendocrine Tumors; Peptides; Radionuclide Imaging; Receptors, Cholecystokinin; Receptors, Somatostatin
PubMed: 34735669
DOI: 10.1007/s11912-021-01139-2