Antitumour Effects of Somatostatin Analogues in the Treatment of Neuroendocrine Tumours

2010 ◽  
Vol 8 (2) ◽  
pp. 94
Author(s):  
Diogo Assed Bastos ◽  
Brenda Gumz ◽  
Frederico Costa ◽  
◽  
◽  
...  
Keyword(s):  
Neuroendocrine Tumours ◽  
Antitumour Activity ◽  
Somatostatin Receptors ◽  
Somatostatin Analogues ◽  
Antiangiogenic Activity ◽  
Tumour Shrinkage ◽  
Phosphotyrosine Phosphatases ◽  
Antitumour Effects

Neuroendocrine tumours (NETs) are rare and heterogeneous neoplasms that can present with functional syndromes due to the hypersecretion of peptides. Somatostatin analogues (SSAs) have been used since the 1980s for the treatment of neuroendocrine tumours, with the aim of controlling the symptoms of functioning tumours and improving patients’ quality of life. Data from preclinical studies offer evidence of both direct and indirect mechanisms by which SSAs can exert antitumour effects. The activation of somatostatin receptors by SSAs leads to the activation of phosphotyrosine phosphatases, which control downstream apoptotic and antiproliferation signalling pathways. Also, the suppression of secretion of several growth factors and inhibition of antiangiogenic activity by SSAs indirectly inhibits tumour cell proliferationin vitro. Previous uncontrolled studies had shown tumour shrinkage and disappearance in response to the SSA octreotide. Recent results from the randomised and placebo-controlled PROMID trial have demonstrated that octreotide has antitumour activity in patients with metastatic mid-gut NETs. This article examines recent data providing evidence of the antitumour activity of somatostatin analogues.

scholarly journals Antitumour Effects of Somatostatin Analogues in the Treatment of Neuroendocrine Tumours

2012 ◽  
Vol 08 (03) ◽  
pp. 156
Author(s):  
Diogo Assed Bastos ◽  
Brenda Gumz ◽  
Frederico Costa ◽  
◽  
◽  
...  
Keyword(s):  
Neuroendocrine Tumours ◽  
Antitumour Activity ◽  
Somatostatin Receptors ◽  
Somatostatin Analogues ◽  
Antiangiogenic Activity ◽  
Tumour Shrinkage ◽  
Phosphotyrosine Phosphatases ◽  
Antitumour Effects

Neuroendocrine tumours (NETs) are rare and heterogeneous neoplasms that can present with functional syndromes due to the hypersecretion of peptides. Somatostatin analogues (SSAs) have been used since the 1980s for the treatment of neuroendocrine tumours, with the aim of controlling the symptoms of functioning tumours and improving patients’ quality of life. Data from preclinical studies offer evidence of both direct and indirect mechanisms by which SSAs can exert antitumour effects. The activation of somatostatin receptors by SSAs leads to the activation of phosphotyrosine phosphatases, which control downstream apoptotic and antiproliferation signalling pathways. Also, the suppression of secretion of several growth factors and inhibition of antiangiogenic activity by SSAs indirectly inhibits tumour cell proliferationin vitro. Previous uncontrolled studies had shown tumour shrinkage and disappearance in response to the SSA octreotide. Recent results from the randomised and placebo-controlled PROMID trial have demonstrated that octreotide has antitumour activity in patients with metastatic mid-gut NETs. This article examines recent data providing evidence of the antitumour activity of somatostatin analogues.

scholarly journals Unresectable Recurrent Multiple Meningioma: A Case Report with Radiological Response to Somatostatin Analogues

2016 ◽  
Vol 9 (2) ◽  
pp. 520-525 ◽  
Author(s):  
Ana Ortolá Buigues ◽  
Irene Crespo Hernández ◽  
Manuela Jorquera Moya ◽  
Jose Ángel Díaz Pérez
Keyword(s):  
Somatostatin Receptors ◽  
Somatostatin Analogues ◽  
Somatostatin Analogue ◽  
Continuous Administration ◽  
Antiangiogenic Effect ◽  
Neurological Improvement ◽  
Radiological Response ◽  
Multiple Meningioma ◽  
Multiple Recurrences

Medical treatment of meningiomas is reserved for cases in which surgery and radiotherapy have failed. Given that a high percentage of meningiomas express somatostatin receptors, treatment with somatostatin analogues has been proposed. In addition, these medications have been shown to have an antiproliferative and antiangiogenic effect in vitro. To date, very few cases with clinical response and none with radiological response have been described. The case described here is the first to report a radiological response. A 76-year-old Caucasian male was first diagnosed with unresectable meningioma at age 47. The patient experienced multiple recurrences and underwent three surgeries and radiotherapy over the years from the initial diagnosis. Despite treatment, the disease continued its progression. Based on an Octreoscan positive for tumour uptake, therapy with extended-release somatostatin analogues was started. Although no clinical neurological improvement was observed, magnetic resonance imaging scans revealed a discreet but continuous radiological response over time. After >2 years of continuous administration of lanreotide, the patient remains progression free. In highly selected cases, somatostatin analogue treatment for meningioma may be beneficial. Based on our findings, treatment with somatostatin analogues should be maintained longer than previously described before evaluating treatment response.

scholarly journals Somatostatin analogues increase AIP expression in somatotropinomas, irrespective of Gsp mutations

2013 ◽  
Vol 20 (5) ◽  
pp. 753-766 ◽  
Author(s):  
Marie-Lise Jaffrain-Rea ◽  
Sandra Rotondi ◽  
Annarita Turchi ◽  
Gianluca Occhi ◽  
Anne Barlier ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Aryl Hydrocarbon Receptor ◽  
Primary Cultures ◽  
Gene Mutations ◽  
Somatostatin Analogues ◽  
Interacting Protein ◽  
Aryl Hydrocarbon ◽  
Tumour Shrinkage ◽  
Suprasellar Extension

Germline aryl hydrocarbon receptor interacting protein (AIP) gene mutations confer a predisposition to pituitary adenoma (PA), predominantly GH-secreting (GH-PA). As recent data suggest a role for AIP in the pathogenesis of sporadic GH-PA and their response to somatostatin analogues (SSA), the expression of AIP and its partner, aryl hydrocarbon receptor (AHR), was determined by semiquantitative immunohistochemistry scoring in 62 sporadic GH-PA (37 treated with SSA preoperatively). The influence ofGspstatus was studied in a subset of tumours (n=39, 14Gsp+) and six GH-PA were available for primary cultures. AIP and AHR were detected in most cases, with a positive correlation between AIP and cytoplasmic AHR (P=0.012). Low AIP expression was significantly more frequent in untreated vs SSA-treated tumours (44.0 vs 20.5%,P=0.016). AHR expression or localisation did not differ between the two groups. Similarly,in vitrooctreotide induced a median twofold increase in AIP expression (range 1.2–13.9,P=0.027) in GH-PA. In SSA-treated tumours, the AIP score was significantly higher in the presence of preoperative IGF1 decrease or tumour shrinkage (P=0.008 andP=0.014 respectively). In untreated tumours, low AIP expression was significantly associated with invasiveness (P=0.028) and suprasellar extension (P=0.019). The only effect ofGspstatus was a significantly lower nuclear AHR score inGsp+vsGsp−tumours (P=0.025), irrespective of SSA. In conclusion, AIP is involved in the aggressiveness of sporadic GH-PA, regardless ofGspstatus, and AIP up-regulation in SSA-treated tumours is associated with a better preoperative response, with no clear role for AHR.

Antitumour activity of somatostatin analogues in progressive metastatic neuroendocrine tumours

2001 ◽  
Vol 37 (8) ◽  
pp. 1014-1019 ◽  
Author(s):  
T Aparicio ◽  
M Ducreux ◽  
E Baudin ◽  
J.-C Sabourin ◽  
T De Baere ◽  
...  
Keyword(s):  
Neuroendocrine Tumours ◽  
Antitumour Activity ◽  
Somatostatin Analogues

scholarly journals GEP–NETs UPDATE: Biotherapy for neuroendocrine tumours

2015 ◽  
Vol 172 (1) ◽  
pp. R31-R46 ◽  
Author(s):  
T Alonso-Gordoa ◽  
J Capdevila ◽  
E Grande
Keyword(s):  
Neuroendocrine Tumours ◽  
Symptomatic Relief ◽  
Somatostatin Receptors ◽  
Treatment Strategies ◽  
Mtor Inhibitors ◽  
Somatostatin Analogues ◽  
Antiangiogenic Agents ◽  
Tumour Control ◽  
Control Growth ◽  
Long Time

Neuroendocrine tumours (NETs) represent a less frequent and heterogeneous group of tumours, which has experienced, in recent years, a significant increase in effective therapeutic possibilities overcoming the disappointing results from chemotherapy. Initial improvements in treatment strategies came from somatostatin analogues (SSAs) that have widely demonstrated a significant improvement in symptomatic relief and tumour control growth by a complex mechanism of action over cell survival, angiogenesis and immunomodulation. Recent investigations have pointed out novel SSAs with a wider binding profile (pasireotide), chimeric molecules against somatostatin receptors and dopamine receptors and the combination with targeted agents, such as mTOR inhibitors or antiangiogenic agents. Immunotherapy is the second cornerstone in NET treatment and has been represented with interferon alpha for a long time, with a demonstrated activity on tumour and clinical response. Its less manageable adverse events have limited its usage. However, different checkpoints in immune system regulation have been effectively targeted in different solid tumours, and novel approaches are currently arising in NETs. In conclusion, biotherapy remains an active treatment strategy for initial approach in patients with NETs. Further investigation on patients' selection, molecular profiles, treatment sequence or combination and optimisation of current and novel biotherapy agents is required.

scholarly journals Recent advances in radiological and radionuclide imaging and therapy of neuroendocrine tumours

2004 ◽  
Vol 151 (1) ◽  
pp. 15-27 ◽  
Author(s):  
G Kaltsas ◽  
A Rockall ◽  
D Papadogias ◽  
R Reznek ◽  
AB Grossman
Keyword(s):  
Chromaffin Cell ◽  
Neuroendocrine Tumours ◽  
Somatostatin Receptors ◽  
Somatostatin Analogues ◽  
Therapeutic Modality ◽  
Response To Treatment ◽  
Helical Computed Tomography ◽  
Positron Emission ◽  
Octreotide Therapy ◽  
Magnetic Resonance Imaging Mri

Neuroendocrine tumours (NETs) constitute a heterogeneous group of tumours that are able to express cell membrane neuroamine uptake mechanisms and/or specific receptors, such as somatostatin receptors, which can be of great value in the localization and treatment of these tumours. Scintigraphy with (111)In-pentetreotide has become one of the most important imaging investigations in the initial identification and staging of gastro-enteropancreatic (GEP) tumours, whereas helical computed tomography (CT), magnetic resonance imaging (MRI), endoscopic and/or peri-operative ultrasonography are used for the precise localization of GEPs and in monitoring their response to treatment. Scintigraphy with (123)I-MIBG (meta-iodobenzylguanidine) is sensitive in the identification of chromaffin cell tumours, although scintigraphy with (111)In-pentetreotide may also have a role in the localization of malignant chromaffin cell tumours and medullary thyroid carcinoma; for further localization and monitoring of the response to treatment both CT and MRI are used with high diagnostic accuracy. More recently, positron emission tomography (PET) scanning is being increasingly used for the localization of NETs, particularly when other imaging modalities have failed, although its precise role and utility remain to be defined. Surgery is still the usual initial therapeutic, and only curative, modality of choice; however, the majority of NETs will require further treatment with somatostatin analogues and/or interferon; chemotherapy may be used for progressive and highly aggressive NETs, but its role has not been clearly defined. For those NETs that demonstrate uptake to a diagnostic scan with (123)I-MIBG or (111)In-octreotide, therapy with radionuclides such as (131)I-MIBG or (111)In/(90)Y-octreotide or other isotopes, presents a further evolving therapeutic modality.

scholarly journals Treatment of advanced neuroendocrine tumours with radiolabelled somatostatin analogues

2005 ◽  
Vol 12 (4) ◽  
pp. 683-699 ◽  
Author(s):  
G A Kaltsas ◽  
D Papadogias ◽  
P Makras ◽  
A B Grossman
Keyword(s):  
Neuroendocrine Tumours ◽  
Performance Status ◽  
Somatostatin Receptors ◽  
Tumour Response ◽  
Somatostatin Analogues ◽  
Symptomatic Improvement ◽  
Tumour Regression ◽  
Somatostatin Analogue ◽  
Tumour Mass ◽  
Pancreatic Islet Cell

Neuroendocrine tumours (NETs) constitute a heterogeneous group of tumours that frequently express cell membrane-specific peptide receptors, such as somatostatin receptors (SSTRs), and of which gastroenteropancreatic (GEP), carcinoid and pancreatic islet cell tumours exhibit the highest expression of SSTRs. Radiolabelled receptor-binding somatostatin analogues (octreotide and lanreotide) act as vehicles to guide radioactivity to tissues expressing SSTRs, and can thus be used for their diagnosis and treatment. After the localization of NETs bearing SSTRs with 111In-octreotide (OctreoScan), a number of radioisotopes with different physical properties have been used for their treatment. The administration of high doses of the Auger electron and γ-emitter 111In-diethylenetriaminepenta-acetic acid (DTPA)0,octreotide in patients with metastatic tumours has been associated with considerable symptomatic improvement but relatively few and short-lived objective tumour responses. The use of another radiolabelled somatostatin analogue coupled with 90Y, a pure β-emitter, 90Y-1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA)0,Tyr3,octreotide (90Y-DOTATOC, OctreoTher), was associated with 10–30% objective tumour response rates, and appears to be particularly effective in larger tumours. 111In- and 90Y-DOTA-lanreotide has also been used for the treatment of NETs although its therapeutic efficacy is probably inferior to that of octreotide-based radiopharmaceuticals. More recently, treatment with 177Lu-DOTA0,Tyr3octreotate (177Lu-DOTATATE), which has a higher affinity for the SSTR subtype 2, resulted in approximately 30% complete or partial tumour responses; this radiopharmaceutical is particularly effective in smaller tumours. Furthermore, treatment using both 90Y-DOTATOC and 177Lu-DOTA0,Tyr3octreotate seems promising, as the combination of these radiopharmaceuticals could be effective in tumours bearing both small and large lesions. Tumour regression is positively correlated with a high level of uptake on 111In-octreotide scintigraphy, limited tumour mass and good performance status. In general, better responses have been obtained in GEP tumours than other NETs. The side effects of this form of therapy are relatively few and mild, particularly when kidney-protective agents are used. Treatment with radiolabelled somatostatin analogues presents a promising tool for the management of patients with inoperable or disseminated NETs, and particularly GEP tumours.

scholarly journals From biology to clinical experience: evolution in the knowledge of neuroendocrine tumours

2011 ◽  
Vol 2 (2) ◽  
pp. 79
Author(s):  
Emilio Bajetta ◽  
Giuseppe Procopio ◽  
Sara Pusceddu ◽  
Filippo Pietrantonio ◽  
Massimo Milione ◽  
...  
Keyword(s):  
Neuroendocrine Tumours ◽  
Clinical Course ◽  
Clinical Investigation ◽  
Target Therapy ◽  
Somatostatin Analogues ◽  
Good Activity ◽  
Multimodal Approach ◽  
Tumour Shrinkage ◽  
Biological Heterogeneity ◽  
Tumour Cell Growth

Neuroendocrine tumours (NETs) represent a group of neoplasias characterized by significant histopathological and biological heterogeneity. Diagnosis of neuroendocrine tumours relies upon histological examination augmented by newer techniques, such as pet-dotatoc scan. Surgery represents the only curative therapeutic approach. In advanced unresectable disease, medical treatment is the best choice. Somatostatin analogues allow adequate control of the carcinoid syndrome with a low effect on tumour cell growth. Chemotherapy has a good activity only in poor prognosis patients. According to the clinical course of the disease, a multimodal approach could be evaluated in selected cases. New target therapy including multikinase inhibitors, monoclonal antibody and m-tor inhibitors is now under clinical investigation for the treatment of advanced NETs. Preliminary results demonstrated a good activity in terms of disease control rate and tumour shrinkage.

The corellation between somatostatin receptors expression and octreotide treatment in non-functioning pituitary adenomas

2016 ◽  
Vol 62 (5) ◽  
pp. 69
Author(s):  
Natalia Bozena Zawada
Keyword(s):  
Pituitary Adenomas ◽  
Tumour Size ◽  
Somatostatin Receptors ◽  
Somatostatin Analogues ◽  
Strong Expression ◽  
Tumour Shrinkage ◽  
Octreotide Treatment ◽  
Control Magnetic Resonance Imaging ◽  
Positive Results ◽  
Non Functioning Pituitary Adenomas

Introduction. Neurosurgery, which is the treatment of choice of non-functioning pituitary adenomas (NFPA), is often incurative. It usually leaves tumour residue that can regrow in the future. There is no established management for the postoperative period of NFPA, however, some data suggest that somatostatin analogues (SSA) can be effective, especially regarding somatostatin receptors (SSTR) presence in NFPA. SSTR scintigraphy and immunohistochemistry are used to assess SSTR expression in NFPA.Aim: to analyse the outcome of SSA treatment in NFPA and to correlate it with the results of SSTR scintigraphy and immunohistochemistry.Material and methods. Twenty six NFPA patients after incomplete neurosurgery with positive results of scintigraphy and immunohistochemistry were included in the study. All patients were treated with octreotide LAR 20mg intramuscular every 4 weeks. The tumour size was evaluated in control magnetic resonance imaging after 2 years of SSA therapy.Results. Tumour size remained stable in the majority of NFPA. Adenoma size reduction was observed in 2 patients with strong expression of SSTR2 in both scintigraphy and immunohistochemistry. Increase of tumour size was noticed in 4 patients whose tumours were characterised not only by the presence of SSTR2 and SSTR5 but also by strong expression of SSTR1 in immunohistochemistry.Conclusions. Only strong expression of SSTR2 can predict patients response to SSA treatment in NFPA. However, strong expression of SSTR1 observed in some of NFPA gives hope that introduction of new broad spectrum SSA like pasireotide would be more effective, especially in tumour shrinkage.

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