scholarly journals Somatostatin receptor ligands and resistance to treatment in pituitary adenomas

2014 ◽  
Vol 52 (3) ◽  
pp. R223-R240 ◽  
Author(s):  
Daniel Cuevas-Ramos ◽  
Maria Fleseriu
Keyword(s):  
Pituitary Adenomas ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Receptor Expression ◽  
Biologically Active ◽  
Imaging Features ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Granulation Pattern ◽  
Acth Secreting

Somatostatin (SST), an inhibitory polypeptide with two biologically active forms SST14 and SST28, inhibits GH, prolactin (PRL), TSH, and ACTH secretion in the anterior pituitary gland. SST also has an antiproliferative effect inducing cell cycle arrest and apoptosis. Such actions are mediated through five G-protein-coupled somatostatin receptors (SSTR): SSTR1–SSTR5. In GH-secreting adenomas, SSTR2 expression predominates, and somatostatin receptor ligands (SRLs; octreotide and lanreotide) directed to SSTR2 are presently the mainstays of medical therapy. However, about half of patients show incomplete biochemical remission, but the definition of resistanceper seremains controversial. We summarize here the determinants of SRL resistance in acromegaly patients, including clinical, imaging features as well as molecular (mutations, SSTR variants, and polymorphisms), and histopathological (granulation pattern, and proteins and receptor expression) predictors. The role of SSTR5 may explain the partial responsiveness to SRLs in patients with adequate SSTR2 density in the cell membrane. In patients with ACTH-secreting pituitary adenomas, i.e. Cushing's disease (CD), SSTR5 is the most abundant receptor expressed and tumors show low SSTR2 density due to hypercortisolism-induced SSTR2 down-regulation. Clinical studies with pasireotide, a multireceptor-targeted SRL with increased SSTR5 activity, lead to approval of pasireotide for treatment of patients with CD. Other SRL delivery modes (oral octreotide), multireceptor-targeted SRL (somatoprim) or chimeric compounds targeting dopamine D2 receptors and SSTR2 (dopastatin), are briefly discussed.

scholarly journals Treatment of Aggressive Pituitary Adenomas: A Case-Based Narrative Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Odelia Cooper ◽  
Vivien Bonert ◽  
Ning-Ai Liu ◽  
Adam N. Mamelak
Keyword(s):  
Radiation Therapy ◽  
Pituitary Adenomas ◽  
Somatostatin Receptor ◽  
Mtor Inhibitors ◽  
Disease Recurrence ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Individualized Approach ◽  
Evidence Based Guidelines

Management of aggressive pituitary adenomas is challenging due to a paucity of rigorous evidence supporting available treatment approaches. Recent guidelines emphasize the need to maximize standard therapies as well as the use of temozolomide and radiation therapy to treat disease recurrence. However, often these adenomas continue to progress over time, necessitating the use of additional targeted therapies which also impact quality of life and long-term outcomes. In this review, we present 9 cases of aggressive pituitary adenomas to illustrate the importance of a multidisciplinary, individualized approach. The timing and rationale for surgery, radiation therapy, temozolomide, somatostatin receptor ligands, and EGFR, VEGF, and mTOR inhibitors in each case are discussed within the context of evidence-based guidelines and clarify strategies for implementing an individualized approach in the management of these difficult-to-treat-adenomas.

Role of somatostatin receptor ligands in the treatment of acromegaly – review of literature

2011 ◽  
Vol 152 (18) ◽  
pp. 715-721 ◽  
Author(s):  
Orsolya Nemes ◽  
Emese Mezősi
Keyword(s):  
Medical Therapy ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Clinical Manifestations ◽  
Oral Glucose ◽  
Receptor Ligands ◽  
Long Term Outcome ◽  
Somatostatin Receptor Ligands

Acromegaly is a rare disease with typical clinical manifestations. Untreated acromegaly carries a 2-4-fold increase in mortality in long-term outcome. The goal of treatment is double, including biochemical control of the disease (normalization of serum IGF1 levels compared to age and gender matched controls, GH levels below 1 ng/ml after oral glucose load, or random GH below 2.5 ng/ml) and control of the tumor mass. The therapeutic modalities currently available for the treatment of acromegaly are: surgery, medical therapy, radiation therapy and their combinations. The cornerstones of medical therapy in acromegaly are the somatostatin receptor ligands due to their effectiveness in controlling GH excess in 60-70 % of patients and their beneficial effects on tumor volume. Somatostatin analogues have an established role as adjuvant therapy after non-curative surgery, and evidence suggests their use as primary treatment for selected patients. The long-term use of somatostatin receptor ligands is safe and they are well tolerated. Future medical therapy consists of pasireotide, a novel, universal somatostatin receptor agonist, and a new class of drugs named dopastatins. The latter so-called chimeric molecules have strong affinity for somatostatin receptors and dopamine-2 receptors, resulting in a more effective blocking of GH secretion, according to preliminary data. The authors of this paper review the current medical therapy of acromegaly, focusing on the role of somatostatin receptor ligands. Orv. Hetil., 2011, 152, 715–721.

scholarly journals High Expression of Somatostatin Receptors 2A, 3, and 5 in Corticotroph Pituitary Adenoma

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Felix Behling ◽  
Jürgen Honegger ◽  
Marco Skardelly ◽  
Irina Gepfner-Tuma ◽  
Ghazaleh Tabatabai ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Pituitary Adenomas ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Somatostatin Analogs ◽  
Receptor Expression ◽  
Cushing's Disease ◽  
Endocrine Tumors ◽  
Nonfunctioning Pituitary Adenomas

The development of somatostatin analogs for the treatment of pituitary Cushing’s disease has been based on somatostatin receptor expression analyses of small cohorts of pituitary adenomas. Additionally, the classification of pituitary adenomas has recently changed. To enable progress with this treatment option, we assessed somatostatin receptors in a large cohort of corticotroph and other pituitary adenomas according to the new WHO classification of endocrine tumors. Paraffin-embedded tumor samples of 88 corticotroph pituitary adenomas and 30 nonadenomatous pituitary biopsies were analyzed after processing into tissue microarrays and immunohistochemical staining for SSTR 1, SSTR2A, SSTR3, SSTR4, and SSTR5. For comparison, 159 other noncorticotroph pituitary adenomas were analyzed. SSTR3 expression was higher in corticotroph adenomas compared to PIT-1-positive, gonadotroph, and nonfunctioning pituitary adenomas (p<0.0001, p=0.0280, and p<0.0001, respectively). This was also the case for the expression of SSTR5 (p=0.0003, p<0.0001, and p<0.0001, respectively). SSTR2A expression was higher compared to gonadotroph and nonfunctioning pituitary adenomas (p=0.0217 and 0.0126, respectively) while PIT-1-positive adenomas showed even higher SSTR2A expression (p<0.0001). SSTR2A and SSTR5 were both expressed higher in nonadenomatous pituitary biopsies than in pituitary adenomas (p=0.0126 and p=0.0008, respectively). There are marked expression differences of SSTR1-5 as well as changes in expression in recurrent disease that need to be addressed when looking for other possible substances for the treatment of Cushing’s disease. SSTR2A, SSTR3, and SSTR5 seem to be most suitable biomarkers for a targeted therapy with somatostatin analogs.

Diverse Peptidyl Privileged Structures as Potent Somatostatin Receptor Ligands

2004 ◽  
Vol 1 (2) ◽  
pp. 121-125 ◽  
Author(s):  
Alexander Pasternak ◽  
Yanping Pan ◽  
Ralph Mosley ◽  
Susan Rohrer ◽  
Elizabeth Birzin ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Privileged Structures

MRI follow‐up of patients with acromegaly treated after surgery with first‐generation somatostatin receptor ligands

2021 ◽  
Author(s):  
Naia Grandgeorge ◽  
Giovanni Barchetti ◽  
Solange Grunenwald ◽  
Fabrice Bonneville ◽  
Philippe Caron
Keyword(s):  
First Generation ◽  
Somatostatin Receptor ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands

Biochemical efficacy of long-acting lanreotide depot/Autogel in patients with acromegaly naïve to somatostatin-receptor ligands: analysis of three multicenter clinical trials

Pituitary ◽  
2018 ◽  
Vol 21 (3) ◽  
pp. 283-289 ◽  
Author(s):  
Hussain Alquraini ◽  
Maria del Pilar Schneider ◽  
Beloo Mirakhur ◽  
Ariel Barkan
Keyword(s):  
Clinical Trials ◽  
Somatostatin Receptor ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Multicenter Clinical Trials ◽  
Long Acting

scholarly journals Treatment of Advanced Hepatocellular Carcinoma with Somatostatin Analogues: A Review of the Literature

2019 ◽  
Vol 20 (19) ◽  
pp. 4811
Author(s):  
Hendrik Reynaert ◽  
Isabelle Colle
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Current Knowledge ◽  
Primary Liver Cancer ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Somatostatin Analogues ◽  
Receptor Expression ◽  
Surrounding Tissue ◽  
Advanced Hepatocellular Carcinoma

Hepatocellular carcinoma, one of the most dreaded complications of cirrhosis, is a frequent cancer with high mortality. Early primary liver cancer can be treated by surgery or ablation techniques, but advanced hepatocellular carcinoma remains a challenge for clinicians. Most of these patients have underlying cirrhosis, which complicates or even precludes treatment. Therefore, efficacious treatments without major side effects are welcomed. Initial results of treatment of advanced hepatocellular carcinoma with somatostatin analogues were promising, but subsequent trials have resulted in conflicting outcomes. This might be explained by different patient populations, differences in dosage and type of treatment and differences in somatostatin receptor expression in the tumor or surrounding tissue. It has been shown that the expression of somatostatin receptors in the tumor might be of importance to select patients who could benefit from treatment with somatostatin analogues. Moreover, somatostatin receptor expression in hepatocellular carcinoma has been shown to correlate with recurrence, prognosis, and survival. In this review, we will summarize the available data on treatment of primary liver cancer with somatostatin analogues and analyze the current knowledge of somatostatin receptor expression in hepatocellular carcinoma and its possible clinical impact.

Molecular determinants of enhanced response to somatostatin receptor ligands after debulking in large GH producing adenomas

2020 ◽  
Author(s):  
Joan Gil ◽  
Montserrat Marqués‐Pamies ◽  
Mireia Jordà ◽  
Carmen Fajardo‐Montañana ◽  
Araceli García‐Martínez ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Molecular Determinants

scholarly journals Maintenance of Acromegaly Control in Patients Switching From Injectable Somatostatin Receptor Ligands to Oral Octreotide

2020 ◽  
Vol 105 (10) ◽  
pp. e3785-e3797 ◽  
Author(s):  
Susan L Samson ◽  
Lisa B Nachtigall ◽  
Maria Fleseriu ◽  
Murray B Gordon ◽  
Marek Bolanowski ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Control Measures ◽  
Double Blind Study ◽  
Efficacy And Safety ◽  
Receptor Ligands ◽  
Biochemical Control ◽  
Phase 3 ◽  
Double Blind ◽  
Somatostatin Receptor Ligands ◽  
End Of Treatment

Abstract Purpose The phase 3 CHIASMA OPTIMAL trial (NCT03252353) evaluated efficacy and safety of oral octreotide capsules (OOCs) in patients with acromegaly who previously demonstrated biochemical control while receiving injectable somatostatin receptor ligands (SRLs). Methods In this double-blind study, patients (N = 56) stratified by prior SRL dose were randomly assigned 1:1 to OOC or placebo for 36 weeks. The primary end point was maintenance of biochemical control at the end of treatment (mean insulin-like growth factor 1 [IGF-1] ≤ 1.0 × upper limit of normal [ULN]; weeks 34 and 36). Time to loss of IGF-1 response and proportion requiring reversion to injectable SRLs were assessed as broader control measures. Results Mean IGF-1 measurements were 0.80 and 0.97 × ULN for OOC and 0.84 and 1.69 × ULN for placebo, at baseline and end of treatment, respectively. Mean growth hormone (GH) changed from 0.66 to 0.60 ng/mL for OOCs and 0.90 to 2.57 ng/mL for placebo. Normalization of IGF-1 levels (≤ 1.0 × ULN) was maintained in 58.2% for OOCs vs 19.4% for placebo (P = .008); GH levels were maintained (&lt; 2.5 ng/mL) in 77.7% for OOC vs 30.4% for placebo (P = .0007). Median time to loss of response (IGF-1 &gt; 1.0 or ≥ 1.3 × ULN definitions) for patients receiving placebo was 16 weeks; for patients receiving OOCs, it was not reached for both definitions during the 36-week trial (P &lt; .0001). Of the patients in the OOC group, 75% completed the trial on oral therapy. The OOC safety profile was consistent with previous SRL experience. Conclusions OOCs may be an effective therapy for patients with acromegaly who previously were treated with injectable SRLs.

T2-weighted MRI signal intensity as a predictor of hormonal and tumoral responses to somatostatin receptor ligands in acromegaly: a perspective

Pituitary ◽  
2017 ◽  
Vol 20 (1) ◽  
pp. 116-120 ◽  
Author(s):  
Iulia Potorac ◽  
Albert Beckers ◽  
Jean-François Bonneville
Keyword(s):  
Signal Intensity ◽  
Somatostatin Receptor ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands
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