Predictors of biochemical response to somatostatin receptor ligands in acromegaly

Marazuela, Mónica; Martínez-Hernandez, Rebeca; Marques-Pamies, Montserrat; Biagetti, Betina; Araujo-Castro, Marta; Puig-Domingo, Manel

doi:10.1016/j.beem.2024.101893

Best Practice & Research Clinical Endocrinology & Metab

2024

DOI: 10.1016/j.beem.2024.101893

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Predictors of biochemical response to somatostatin receptor ligands in acromegaly

Mónica Marazuela,

Rebeca Martínez-Hernandez,

Montserrat Marques-Pamies

et al.

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2024

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Cited by 3 publications

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The place of pasireotide in precision treatment of patients with acromegaly

Pronin,

Alexeeva,

Pronin

et al. 2024

Medicinskij sovet

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Due to the syndromal nature of acromegaly, the effectiveness of its treatment depends on the consideration of age, clinical and pathomorphological features of the disease, which determine the logistics of the selection of personalized therapeutic measures. The disadvantage of the used empirical pharmacotherapy scheme with the help of the ‘trial and error’ method is the formal prescription of drugs without taking into account the peculiarities of the morphofunctional status of the supervised GH-secreting tumors and the targeting of drugs. The lack of differentiated approach to acromegaly treatment is accompanied by a high percentage of therapeutic failures, and also deliberately deprives a significant proportion of patients of the opportunity to achieve timely and safe control of the disease and improve the quality of life. The review presents a comparative analysis of modern drugs used in acromegaly with a focus on the clinical efficacy of the second-generation somatostatin receptor ligand – pasireotide. The mechanism of action and pharmacotherapeutic possibilities of pasireotide LAR are considered. The therapeutic niche for this drug is patients with the presence of sparsely granulated somatotrophic tumor (SGST), characterized by aggressive course, tendency to recurrence and refractoriness to therapy with first-generation somatostatin receptor ligands.Implementation of a precision approach using clinical, morphological, radiological and functional predictors allows not only to identify the specific morphotype of somatotrophic tumor, but also to predict the efficacy of the planned treatment. A table of multidirectional biomarkers of long-term sensitivity of tumor cells to first- and second-generation somatostatin receptor ligands is presented. When SGST, large size of the residual tumor and poor expression of the 2nd subtype of somatostatin receptors are detected, pasireotide LAR can be used as a 1st-line treatment, in both mono- and combination therapy with pegvisomant. Special caution is required when treating patients with diabetes mellitus or predisposition to its development. The paper discusses in detail the measures aimed at prevention, dynamic control and correction of pasireotide-associated hyperglycemia.

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The place of pasireotide in precision treatment of patients with acromegaly

Pronin,

Alexeeva,

Pronin

et al. 2024

Medicinskij sovet

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Predicting Response to Medical Treatment in Acromegaly via Granulation Pattern, Expression of Somatostatin Receptors Type 2 and 5 and E-Cadherin

Gliga,

Chinezu,

Pascanu

2024

IJMS

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Resistance to first-generation somatostatin receptor ligand (fgSRL) treatment in acromegaly is common, making the identification of biomarkers that predict fgSRL response a desired goal. We conducted a retrospective analysis on 21 patients with acromegaly who underwent surgery and subsequent pharmacological treatment. Through immunohistochemistry (IHC), we assessed the expression of the somatostatin receptor subtypes SSTR2 and SSTR5, E-Cadherin, and cytokeratin granulation pattern (sparsely or densely). Patients were divided into responders and non-responders based on their biochemical response to fgSRL and/or the newer agent, Pasireotide, or the GH-blocker, Pegvisomant. Patients resistant to fgSRL (n = 12) exhibited lower SSTR2 and E-Cadherin expressions. Sparsely granulated tumors were more frequent in the non-responder group. SSTR2 (p = 0.024, r = 0.49) and E-Cadherin (p = 0.009, r = 0.64) positively correlated with the Insulin-like Growth Factor 1 (IGF-1) decrease after fgSRL, while SSTR5 (p = 0.107, r = −0.37) showed a trend towards negative correlation. SSTR5 positivity seemed to be associated with Pasireotide response, albeit the number of treated patients was too low (n = 4). No IHC markers correlated with Pegvisomant response. Our findings suggest that densely granulated tumors, with positive SSTR2 and E-Cadherin seem to be associated with favorable fgSRL responses. The strongest predictive value of the studied markers was found for E-Cadherin, which seems to surpass even SSTR2.

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Biochemical Control in a Colombian Cohort of Patients With Acromegaly: A 12-Month Follow-Up Study (2017-2023)

Abreu Lomba,

Corredor-Rengifo,

Mejia Velez

et al. 2024

Cureus

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Predictors of biochemical response to somatostatin receptor ligands in acromegaly

Cited by 3 publications

References 109 publications

The place of pasireotide in precision treatment of patients with acromegaly

The place of pasireotide in precision treatment of patients with acromegaly

Predicting Response to Medical Treatment in Acromegaly via Granulation Pattern, Expression of Somatostatin Receptors Type 2 and 5 and E-Cadherin

Biochemical Control in a Colombian Cohort of Patients With Acromegaly: A 12-Month Follow-Up Study (2017-2023)

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