Radiotherapy Plus the Neurokinin-1 Receptor Antagonist Aprepitant: A Potent Therapeutic Strategy for the Treatment of Diffuse Intrinsic Pontine Glioma

(This article belongs to the Special Issue Outcomes in Glioblastoma Patients: From Diagnosis to Palliation).

Detalles Bibliográficos
Autores: Muñoz, Miguel, Rosso, Marisa
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/391535
Acceso en línea:http://hdl.handle.net/10261/391535
https://api.elsevier.com/content/abstract/scopus_id/85217570722
Access Level:acceso abierto
Palabra clave:DIPG
Angiogenesis
Antitumor
Apoptosis
Aprepitant
Glioma
Metastases
Neurokinin-1 receptor
Substance P
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spelling Radiotherapy Plus the Neurokinin-1 Receptor Antagonist Aprepitant: A Potent Therapeutic Strategy for the Treatment of Diffuse Intrinsic Pontine GliomaMuñoz, MiguelRosso, MarisaDIPGAngiogenesisAntitumorApoptosisAprepitantGliomaMetastasesNeurokinin-1 receptorSubstance P(This article belongs to the Special Issue Outcomes in Glioblastoma Patients: From Diagnosis to Palliation).[Simple Summary] Diffuse intrinsic pontine glioma (DIPG) is a devastating childhood brain tumor. The median survival of DIPG is 16 to 24 months, regardless of the treatment received. Therefore, new therapeutic strategies against DIPG are urgently needed. The peptide substance P (SP), through the neurokinin-1 receptor (NK-1R), is involved in glioma progression. Furthermore, all glioma cells express NK-1R, and NK-1R is essential for glioma cell viability. In contrast, NK-1R antagonists, such as the drug aprepitant, penetrate the brain and counteract all the pathophysiological effects produced by SP in glioma. The combination of radiotherapy with NK-1R antagonists produces radiosensitization and radioneuroprotection. This review updates the involvement of the SP/NK-1R system in glioma progression and the clinical application of NK-1R antagonist drugs in DIPG therapy. NK-1R plays a crucial role in glioma progression and NK-1R antagonists such as aprepitant could be used in combination with radiotherapy as a therapeutic strategy for DIPG patients.[Background] Diffuse intrinsic pontine glioma (DIPG) is a devastating childhood brainstem tumor. The median survival of DIPG is 16–24 months independent of the treatment received. Therefore, new therapeutic strategies against DIPG are urgently needed. Substance P (SP) peptide, through the neurokinin neurokinin-1 receptor (NK-1R), is involved in glioma progression. It induces glioma cell proliferation by activating MAPKs (p38 MAPK, ERK1/2, and JNK), c-Myc, AP-1, and NF-κB and induces antiapoptotic effects via PI3K/Akt/mTOR in glioma cells. SP favors glycogen breakdown that is essential for glycolysis. The SP/NK-1R system also regulates the migration and invasion of glioma cells, stimulates angiogenesis, and triggers inflammation which contributes to glioma progression. Moreover, all glioma cells express NK-1R, and NK-1R is essential for the viability of glioma cells and not of normal cells. In contrast, in glioma, NK-1R antagonists, such as the drug aprepitant, penetrate the brain and reach therapeutic concentrations, thereby inhibiting mitogenesis, inducing apoptosis, and inhibiting the breakdown of glycogen in glioma cells. In addition, they inhibit angiogenesis and exert antimetastatic and anti-inflammatory effects. The combination of radiotherapy with NK-1R antagonists produces radiosensitization and radioneuroprotection, reduces both peritumoral- and radiation-induced inflammation, and also provides antinausea and antivomiting effects. Objective: This review updates the involvement of the SP/NK-1R system in glioma promotion and progression and the potential clinical application of NK-1R antagonist drugs in DIPG therapy. Conclusions: NK-1R plays a crucial role in glioma progression and NK-1R antagonists such as aprepitant could be used in combination with radiotherapy as a potent therapeutic strategy for the treatment of patients with DIPG.This research received no external funding.Peer reviewedMultidisciplinary Digital Publishing InstituteMuñoz, Miguel [0000-0002-2853-8481]Rosso, Marisa 0000-0001-7587-0025]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_dcae04bcPublisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/391535https://api.elsevier.com/content/abstract/scopus_id/85217570722reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.3390/cancers17030520Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3915352026-05-22T06:33:51Z
dc.title.none.fl_str_mv Radiotherapy Plus the Neurokinin-1 Receptor Antagonist Aprepitant: A Potent Therapeutic Strategy for the Treatment of Diffuse Intrinsic Pontine Glioma
title Radiotherapy Plus the Neurokinin-1 Receptor Antagonist Aprepitant: A Potent Therapeutic Strategy for the Treatment of Diffuse Intrinsic Pontine Glioma
spellingShingle Radiotherapy Plus the Neurokinin-1 Receptor Antagonist Aprepitant: A Potent Therapeutic Strategy for the Treatment of Diffuse Intrinsic Pontine Glioma
Muñoz, Miguel
DIPG
Angiogenesis
Antitumor
Apoptosis
Aprepitant
Glioma
Metastases
Neurokinin-1 receptor
Substance P
title_short Radiotherapy Plus the Neurokinin-1 Receptor Antagonist Aprepitant: A Potent Therapeutic Strategy for the Treatment of Diffuse Intrinsic Pontine Glioma
title_full Radiotherapy Plus the Neurokinin-1 Receptor Antagonist Aprepitant: A Potent Therapeutic Strategy for the Treatment of Diffuse Intrinsic Pontine Glioma
title_fullStr Radiotherapy Plus the Neurokinin-1 Receptor Antagonist Aprepitant: A Potent Therapeutic Strategy for the Treatment of Diffuse Intrinsic Pontine Glioma
title_full_unstemmed Radiotherapy Plus the Neurokinin-1 Receptor Antagonist Aprepitant: A Potent Therapeutic Strategy for the Treatment of Diffuse Intrinsic Pontine Glioma
title_sort Radiotherapy Plus the Neurokinin-1 Receptor Antagonist Aprepitant: A Potent Therapeutic Strategy for the Treatment of Diffuse Intrinsic Pontine Glioma
dc.creator.none.fl_str_mv Muñoz, Miguel
Rosso, Marisa
author Muñoz, Miguel
author_facet Muñoz, Miguel
Rosso, Marisa
author_role author
author2 Rosso, Marisa
author2_role author
dc.contributor.none.fl_str_mv Muñoz, Miguel [0000-0002-2853-8481]
Rosso, Marisa 0000-0001-7587-0025]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv DIPG
Angiogenesis
Antitumor
Apoptosis
Aprepitant
Glioma
Metastases
Neurokinin-1 receptor
Substance P
topic DIPG
Angiogenesis
Antitumor
Apoptosis
Aprepitant
Glioma
Metastases
Neurokinin-1 receptor
Substance P
description (This article belongs to the Special Issue Outcomes in Glioblastoma Patients: From Diagnosis to Palliation).
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_dcae04bc
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/391535
https://api.elsevier.com/content/abstract/scopus_id/85217570722
url http://hdl.handle.net/10261/391535
https://api.elsevier.com/content/abstract/scopus_id/85217570722
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.3390/cancers17030520
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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