Evidence map›Paper›PMID 42177741›Full record

ArticleDrugs in R&D2026

A Combination of the Tryptophan Hydroxylase Inhibitor Telotristat with the mTOR Inhibitor Everolimus as an Effective Strategy Against Neuroendocrine Tumors.

Javier Molina-Cerrillo, Arantzazu Sierra-Ramirez, José L López-Aceituno, Marinela Méndez-Pertuz, Teresa Alonso-Gordoa, Michael Linnebacher, Matteo Santoni, Pablo J Fernandez-Marcos, Enrique Grande

Abstract read
In one paragraph

Article in Drugs in R&D, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

9 authors.

Javier Molina-Cerrillo *Medical Oncology Department, Hospital Universitario Ramón y Cajal, 28034, Madrid, Spain. Javier.molinace@gmail.com.ORCID http://orcid.org/0000-0003-4616-0598
Arantzazu Sierra-Ramirez *Metabolic Syndrome Group-BIOPROMET, Madrid Institute for Advanced Studies-IMDEA Food, CEI UAM+CSIC, 8, Cantoblanco Road, 28049, Madrid, Spain.
José L López-AceitunoMetabolic Syndrome Group-BIOPROMET, Madrid Institute for Advanced Studies-IMDEA Food, CEI UAM+CSIC, 8, Cantoblanco Road, 28049, Madrid, Spain.
Marinela Méndez-PertuzCNIO Cancer Center, Madrid, Spain.
Teresa Alonso-GordoaMedical Oncology Department, Hospital Universitario Ramón y Cajal, 28034, Madrid, Spain.
Michael LinnebacherDepartment of General Surgery, Section of Molecular Oncology and Immunotherapy, University of Rostock, 18055, Rostock, Germany.
Matteo SantoniMedical Oncology Unit, Macerata Hospital, Macerata, Italy.
Pablo J Fernandez-MarcosMetabolic Syndrome Group-BIOPROMET, Madrid Institute for Advanced Studies-IMDEA Food, CEI UAM+CSIC, 8, Cantoblanco Road, 28049, Madrid, Spain. pablojose.fernandez@imdea.org.
Enrique GrandeMedical Oncology Department, MD Anderson Cancer Center Madrid, 28033, Madrid, Spain. egrande@oncomadrid.com.

Funding

GETNE GETNE1716
6 · The paper itself

Abstract

BACKGROUND AND

objectivesNeuroendocrine tumors are a rare and heterogeneous group of neoplasms that frequently cause carcinoid syndrome, characterized by diarrhea, flushing, and carcinoid heart disease. A recent therapy for carcinoid syndrome involves inhibition of tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, using telotristat ethyl. Telotristat has demonstrated clinical control of carcinoid syndrome; however, its potential antitumoral effects remain unclear. This study aimed to evaluate the antitumor activity of telotristat ethyl alone and in combination with everolimus in neuroendocrine tumor models.

methodsCell viability was assessed in three neuroendocrine tumor cell lines of pancreatic (BON-1, QGP-1) and intestinal (HROC57) origin following treatment with telotristat ethyl. Combination treatments with telotristat ethyl and everolimus or other antitumoral agents were evaluated for effects on cell viability, apoptosis, and cell cycle distribution. In vivo efficacy was examined in nude mice bearing BON-1-derived xenografts treated with telotristat ethyl, everolimus, or the combination. Tumor growth, toxicity, proliferation (Ki67), and apoptosis (active caspase-3) were analyzed.

resultsTelotristat ethyl reduced cell viability in all three neuroendocrine tumor cell lines. Combination with everolimus, but not with other antitumoral treatments, synergistically decreased cell viability, induced apoptosis, and reduced the proportion of cells in the G2/M phase. In nude mice bearing BON-1 xenografts, combined treatment with telotristat ethyl and everolimus arrested tumor growth without signs of toxicity compared with single treatments. At the end of treatment, tumors from combination-treated mice showed a reduction in proliferation (Ki67) comparable to single-treated groups and an increase in apoptosis as indicated by active caspase-3.

conclusionsTelotristat ethyl exhibits antitumoral activity in neuroendocrine tumor models in vivo. Moreover, the combination of telotristat ethyl and everolimus, two therapies already used in clinical practice, may represent a safe and effective therapeutic strategy for neuroendocrine tumors.

Indexed as

Antineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsEverolimusMTOR InhibitorsNeuroendocrine TumorsPhenylalaninePyrimidinesTryptophan HydroxylaseAnimalsApoptosisCell Line, TumorCell ProliferationCell SurvivalFemaleHumansMiceAntineoplastic AgentsEverolimusMTOR InhibitorsPhenylalaninePyrimidinestelotristat ethylTryptophan Hydroxylase

Identifiers

PMID42177741
PMCPMC13433658

What Socratic holds

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LicenceCC BY-NC
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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 Socratic graph.