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The novel SSTR3 full agonist ITF2984 shows antitumor properties against pancreatic neuroendocrine tumors (Pan-NETs).
Neuroendocrinology, DOI: 10.1159/000543136 (2024)
BACKGROUND: Somatostatin analogs (SSAs) binding to and activating somatostatin receptors (SSTRs) have been extensively used for the treatment of neuroendocrine tumors (NETs). The currently approved synthetic SSAs have high affinity for SSTR2 (octreotide/lanreotide), or for SSTR2 and SSTR5 (pasireotide). These agents have shown symptoms control and antiproliferative effects in subsets of NET patients and this was associated to the expression of the targeted SSTRs. Pancreatic NETs (Pan-NETs) are uncommon tumors with a propensity to metastasize. For unresectable advanced Pan-NETs expressing SSTRs, SSAs are the first-line medical therapy. Pan-NETs express mainly SSTR1, SSTR2 and SSTR3 and thus should respond to agonists targeting SSTR3. SUMMARY: We evaluated the efficacy of ITF2984, a novel multireceptor agonist with specificity for SSTR3, against Pan-NET cells representative of well differentiated, functioning tumors, and expressing high levels of SSTR3. The effect of ITF2984 on cell proliferation/viability, and on its ability to promote apoptosis and suppress hormone secretion was evaluated in 2D and 3D organotypic culture systems. Pasireotide was tested in parallel for comparative purposes. KEY MESSAGE: We found that ITF2984 is as effective as pasireotide at inhibiting both proliferation/viability and hormone secretion, as well as at inducing apoptosis of Pan-NET cells grown as both 2D monolayers and 3D spheroids. High-dose ITF2984 elicits structural alterations in Pan-NET 3D spheroids compatible with cell death more effectively than pasireotide. Altogether, ITF2984 may represent a useful alternative to pasireotide for the medical treatment of Pan-NETs and other tumors with elevated SSTR3 expression.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Pancreatic neuroendocrine tumors; Somatostatin agonists; Somatostatin receptor 3; ITF2984; Enets Consensus Guidelines; Somatostatin Receptors; In-vivo; Expression; Pasireotide; Trafficking; Management; Adenomas; Som230; Growth
Language
english
Publication Year
2024
HGF-reported in Year
2024
ISSN (print) / ISBN
0028-3835
e-ISSN
1423-0194
Journal
Neuroendocrinology
Publisher
Karger
Publishing Place
Allschwilerstrasse 10, Ch-4009 Basel, Switzerland
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Cancer (IDC)
POF-Topic(s)
30201 - Metabolic Health
Research field(s)
Helmholtz Diabetes Center
PSP Element(s)
G-502590-001
Grants
Italfarmaco
WOS ID
001415461300001
Scopus ID
85218080586
PubMed ID
39733775
Erfassungsdatum
2025-01-17