An Immunohistochemical Investigation of the Expression of Somatostatin Receptor Subtypes – Should Therapeutic Trials be Performed to Determine the Efficacy of Somatostatin Analogs in Treating Advanced Thyroid Malignances?

Pisarek, Hanna; Pawlikowski, Marek; Marchlewska, Magdalena; Minias, Radosław; Winczyk, Katarzyna

doi:10.1055/s-0035-1548825

Cited by 8 publications

(5 citation statements)

References 34 publications

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“…SSTR is frequently expressed in thyroid cancer, with SSTR1 being the most commonly expressed in up to 88.8% of cases while SSTR2 is expressed in 44% of cases. [8, 12] We confirmed that all SSTR subtypes including SSTR4 are expressed in our panel of thyroid cancer cell lines both by Western blot and by immunofluorescence that is able to detect native receptor expression on the intact cell membranes (Fig 3). SSTR2 showed the highest intensity of staining of all the 5 subtypes by immunofluorescence in 5 of the 6 cell lines.…”

Section: Discussionsupporting

confidence: 76%

“…This effect is mediated in part through the inhibition of PI3K/AKT signaling pathway, which is upstream of mTOR intracellular signaling cascade. Similar to other endocrine tumors, various SSTR subtypes are frequently expressed in normal and malignant thyroid epithelial cells where it has inhibitory effect on cell growth and function [6–12]. Aberrant TSH stimulated signaling in thyroid cancers is key to the increased proliferation and survival [13].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of preclinical efficacy of everolimus and pasireotide in thyroid cancer cell lines and xenograft models

et al. 2019

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Background Signaling through mTOR and somatostatin pathway is implicated in thyroid cancer development. Method We evaluated everolimus, an mTOR inhibitor and pasireotide, a multi receptor somatostatin analogue as potential therapy of thyroid cancer focusing on the in vitro and in vivo efficacy, as well as possible mechanism to explain any observed interaction. Results Both everolimus and pasireotide inhibit the growth of thyroid cancer cell lines in vitro with varied efficacy that correlates with tumor origin and somatostatin receptor (SSTR) expression profile of the cell lines. In vitro activity of everolimus show positive correlation with the expression of SSTR types 1, 4 and 5 (CC: 0.9; 0.85, 0.87) while pasireotide activity show negative correlation with SSTR2 (CC: -0.87). Although there is greater modulation of pS6 when pasireotide is combined with everolimus, there is no significant abrogation of the expected feedback upregulation of AKT induced by everolimus. Also, the combination is not significantly better than each agent alone in short and long term in vitro assays. Continuous administration of everolimus at a low dose as opposed to high intermittent dosing schedule has greater antitumor efficacy against thyroid cancer xenografts in vivo . Pasireotide LAR has modest in vivo efficacy and the combination of everolimus and pasireotide LAR achieve greater tumor growth inhibition than each agent alone in TPC-1 xenograft model of thyroid cancer (p = 0.048). Conclusion Our findings provide support for the clinical evaluation of everolimus and pasireotide in thyroid cancer and other neuroendocrine tumors.

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Section: Discussionsupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Evaluation of preclinical efficacy of everolimus and pasireotide in thyroid cancer cell lines and xenograft models

et al. 2019

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“…Medical treatment of endocrine pituitary tumors with somatostatin analogs depends on somatostatin receptor (SSTR) expression [8,9]. SSTR is expressed in both normal and neoplastic human pituitary cells, and SSTR2 and SSTR5 predominate [10,11], but the characteristic expression pattern of SSTR subtypes in pituitary adenomas is tissue-specific and subtype-specific [12]. The therapeutic effects on pituitary adenomas of somatostatin analogs like octreotide and lanreotide depends on the expression of specific somatostatin receptors on the target cells [13,14].…”

Section: Introductionmentioning

confidence: 99%

“…To the best of our knowledge, the expression of SSTR2 and SSTR5 in TSHoma has been demonstrated by IHC in only a few patients [21]. Highly specific antibodies can confirm the expression of SSTR subtype proteins, but heterogeneity of tumors and the use of different detection methods often lead to inconsistency in the reported expression of SSTR subtypes in different types of pituitary tumors [12,21–26]. Because it is clinically meaningful to identify the expression profiles of SSTR subtypes in pituitary adenomas, we investigated the expression of SSTR2 and SSTR5 in a series of patients with TSHoma and other pituitary adenomas, as well as the association of SSTRs expression with efficacy of short-term OCT treatment.…”

Section: Introductionmentioning

confidence: 99%

Clinical Importance of Somatostatin Receptor 2 (SSTR2) and Somatostatin Receptor 5 (SSTR5) Expression in Thyrotropin-Producing Pituitary Adenoma (TSHoma)

Zhang

Song

et al. 2017

Med Sci Monit

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BackgroundThyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism. Somatostatin analogs have proved to be effective for inhibiting pituitary hormones secretion, working via interactions with somatostatin receptors (SSTRs). Moreover, antiproliferative activity of somatostatin analog is now demonstrated in several studies. In the present study, we determined the relative predominance of SSTR2 and SSTR5 subtypes among the different types of adenomas, especially TSHoma, and investigated the relationship between efficacy of short-term octreotide (OCT) treatment and SSTR expression.Material/MethodsSerum hormone determinations and histological findings in resected tissue resulted in 5 diagnoses: 16 TSHomas, 8 acromegaly, 3 prolactinomas, 3 corticotropinomas, 4 clinically nonfunctioning adenomas (NFPAs), and 4 normal pituitary specimens. IHC was performed on formalin-fixed and paraffin-embedded tissue in tissue microarrays.ResultsIHC of SSTR subtypes in the different cohorts showed SSTR2 staining intensity scores higher than SSTR5 in TSHoma, acromegaly and prolactinoma, whereas the expression of SSTR5 was stronger than SSTR2 in corticotropinoma and NFPA. SSTR2 and SSTR5 expressions were significantly higher in TSHoma than in other pituitary adenomas. OCT treatment for a median of 8.4 days (range: 3–18 days) and with a total median dose of 1.9 mg (range: 0.9–4.2 mg) showed a significant decrease of thyroid hormone levels (TSH [μIU/ml] in all patients. Patients with low SSTR5 expression presented a significantly higher TSH suppression rate (P values <0.05).ConclusionsThe present data confirm that somatostatin analogs should be considered as a medical alternative to surgical treatment, especially in patients with TSHoma, and short-term response to OCT therapy may be related to the expression of SSTR5.

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“…Particularly DTCs may demonstrate varied SSTR subtype expressions as opposed to NETs, which commonly express SSTR2 ( 51 ). While several studies have demonstrated SSTR2 positivity in thyroid cancers, other studies have demonstrated a relative abundance of other SSTR subtypes, such as SSTR5, in these tumors ( 62 , 66 , 109 , 125 ). These findings highlight the importance of developing PRRTs based on SSAs that could target SSTRs apart from the SSTR2 subtype.…”

Section: Future Directionsmentioning

confidence: 93%

Peptide Receptor Radionuclide Therapy in Thyroid Cancer

2022

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The treatment options that are currently available for management of metastatic, progressive radioactive iodine (RAI)-refractory differentiated thyroid cancers (DTCs), and medullary thyroid cancers (MTCs) are limited. While there are several systemic targeted therapies, such as tyrosine kinase inhibitors, that are being evaluated and implemented in the treatment of these cancers, such therapies are associated with serious, sometimes life-threatening, adverse events. Peptide receptor radionuclide therapy (PRRT) has the potential to be an effective and safe modality for treating patients with somatostatin receptor (SSTR)+ RAI-refractory DTCs and MTCs. MTCs and certain sub-types of RAI-refractory DTCs, such as Hürthle cell cancers which are less responsive to conventional modalities of treatment, have demonstrated a favorable response to treatment with PRRT. While the current literature offers hope for utilization of PRRT in thyroid cancer, several areas of this field remain to be investigated further, especially head-to-head comparisons with other systemic targeted therapies. In this review, we provide a comprehensive outlook on the current translational and clinical data on the use of various PRRTs, including diagnostic utility of somatostatin analogs, theranostic properties of PRRT, and the potential areas for future research.

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An Immunohistochemical Investigation of the Expression of Somatostatin Receptor Subtypes – Should Therapeutic Trials be Performed to Determine the Efficacy of Somatostatin Analogs in Treating Advanced Thyroid Malignances?

Abstract: The somatostatin multiligand analogs or selective agonists could be considered alternatives to conventional therapeutic agents in aggressive thyroid tumors.

Cited by 8 publications

References 34 publications

Evaluation of preclinical efficacy of everolimus and pasireotide in thyroid cancer cell lines and xenograft models

Evaluation of preclinical efficacy of everolimus and pasireotide in thyroid cancer cell lines and xenograft models

Clinical Importance of Somatostatin Receptor 2 (SSTR2) and Somatostatin Receptor 5 (SSTR5) Expression in Thyrotropin-Producing Pituitary Adenoma (TSHoma)

Peptide Receptor Radionuclide Therapy in Thyroid Cancer

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