Evidence map›Paper›PMID 39996718›Full record

ReviewCells2025

"Cold" Somatostatin Analogs in Neuroendocrine Neoplasms: Decoding Mechanisms, Overcoming Resistance, and Shaping the Future of Therapy.

Sara Massironi, Manuela Albertelli, Iderina Hasballa, Piero Paravani, Diego Ferone, Antongiulio Faggiano, Silvio Danese

Abstract readReview
In one paragraph

Review in Cells, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Trial
  2. Article
  3. Esophageal Perforation in Zollinger-Ellison Syndrome: A Scoping Review of Management and Outcomes.JGH open : an open access journal of gastroenterology and hepatology · 2026
    Review
  4. Article
  5. Review
  6. Article
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Sara MassironiFaculty of Medicine and Surgery, Vita e Salute San Raffaele University, Via Olgettina, 20132 Milan, Italy.ORCID 0000-0003-3214-8192
Manuela AlbertelliEndocrinology, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, 16132 Genova, Italy.
Iderina HasballaEndocrinology, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, 16132 Genova, Italy.
Piero ParavaniUnit of Endocrinology, Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sant'Andrea Hospital, Sapienza University, 00189 Rome, Italy.
Diego FeroneEndocrinology, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, 16132 Genova, Italy.
Antongiulio FaggianoUnit of Endocrinology, Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sant'Andrea Hospital, Sapienza University, 00189 Rome, Italy.ORCID 0000-0002-9324-3946
Silvio DaneseFaculty of Medicine and Surgery, Vita e Salute San Raffaele University, Via Olgettina, 20132 Milan, Italy.ORCID 0000-0001-7341-1351

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNeuroendocrine neoplasms (NENs) represent a heterogeneous group of tumors that pose significant therapeutic challenges due to their potential for progression, metastasis, and hormonal syndromes. Somatostatin analogs (SSAs) have emerged as a cornerstone in NEN treatment, offering both antisecretory and antiproliferative effects by targeting somatostatin receptors (SSTRs). Despite their proven efficacy, intrinsic and acquired resistance mechanisms, including receptor downregulation, tumor heterogeneity, and microenvironmental influences, limit their long-term effectiveness. Recent advances, including high-dose SSA regimens and novel formulations, have aimed to optimize their therapeutic utility and address these limitations. Body of the review. This review explores the cellular and molecular mechanisms underlying the antitumor effects of SSAs, including receptor-mediated signaling pathways, cell cycle arrest, apoptosis induction, and antiangiogenesis. The role of SSAs in combination therapies with mTOR inhibitors and peptide receptor radionuclide therapy (PRRT) is analyzed, emphasizing their synergistic potential. Key clinical trials, such as RADIANT-2, EVERLAR, and NETTER-1, support the efficacy of these approaches, demonstrating improved outcomes when SSAs are combined with targeted agents or radiolabeled therapies. Emerging strategies include high-dose SSA regimens, particularly in progressive cases with low Ki67 indices. Finally, novel formulations, including oral octreotide, paltusotine, and subcutaneous depot formulations like CAM2029, offer improved pharmacokinetics, bioavailability, and patient adherence. Ongoing clinical trials, including SORENTO, further evaluate their efficacy and safety profiles.

conclusionsThis paper provides a comprehensive analysis of the cellular and molecular mechanisms of SSAs. SSAs remain integral to the management of NENs, providing effective tumor stabilization and symptom control. However, resistance mechanisms and tumor heterogeneity necessitate innovative approaches, including high-dose regimens, combination strategies, and next-generation formulations. Future research should focus on refining these strategies to optimize patient outcomes, enhance long-term efficacy, and expand the therapeutic landscape for NENs.

Indexed as

Drug Resistance, NeoplasmNeuroendocrine TumorsSomatostatinAnimalsHumansReceptors, SomatostatinReceptors, SomatostatinSomatostatinhigh-dose SSA therapyneuroendocrine neoplasms (NENs)peptide receptor radionuclide therapy (PRRT)somatostatin analogs (SSAs)somatostatin receptors (SSTRs)

Identifiers

PMID39996718
PMCPMC11854070

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.