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Signaling Pathways mTOR and ERK as Therapeutic Targets in Sinonasal Intestinal-Type Adenocarcinoma

Despite advances in surgery and radiotherapy, the overall prognosis of sinonasal intestinal-type adenocarcinoma (ITAC) is poor, and new treatment options are needed. Recent studies have indicated alterations in cellular signaling pathways that may serve as targets for modern inhibitors. Our aim was...

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Autores principales: Codina-Martínez, Helena, Lorenzo-Guerra, Sara Lucila, Cabal, Virginia N., García-Marín, Rocío, Suárez-Fernández, Laura, Vivanco, Blanca, Sánchez-Fernández, Paula, López, Fernando, Llorente, José Luis, Hermsen, Mario A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10606341/
https://www.ncbi.nlm.nih.gov/pubmed/37894790
http://dx.doi.org/10.3390/ijms242015110
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author Codina-Martínez, Helena
Lorenzo-Guerra, Sara Lucila
Cabal, Virginia N.
García-Marín, Rocío
Suárez-Fernández, Laura
Vivanco, Blanca
Sánchez-Fernández, Paula
López, Fernando
Llorente, José Luis
Hermsen, Mario A.
author_facet Codina-Martínez, Helena
Lorenzo-Guerra, Sara Lucila
Cabal, Virginia N.
García-Marín, Rocío
Suárez-Fernández, Laura
Vivanco, Blanca
Sánchez-Fernández, Paula
López, Fernando
Llorente, José Luis
Hermsen, Mario A.
author_sort Codina-Martínez, Helena
collection PubMed
description Despite advances in surgery and radiotherapy, the overall prognosis of sinonasal intestinal-type adenocarcinoma (ITAC) is poor, and new treatment options are needed. Recent studies have indicated alterations in cellular signaling pathways that may serve as targets for modern inhibitors. Our aim was to evaluate the frequency of mTOR and ERK pathway upregulation in a retrospective series of 139 ITAC and to test the efficacy and mechanism of action of candidate targeted inhibitors in cell line ITAC-3. An immunohistochemical analysis on p-AKT, p-mTOR, p-S6, p-4E-BP1, and p-ERK indicated, respectively, a 68% and 57% mTOR and ERK pathway activation. In vitro studies using low doses of mTOR inhibitor everolimus and ERK inhibitor selumetinib showed significant growth inhibition as monotherapy and especially as combined therapy. This effect was accompanied by the downregulation of mTOR and ERK protein expression. Our data open a new and promising possibility for personalized treatment of ITAC patients.
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spelling pubmed-106063412023-10-28 Signaling Pathways mTOR and ERK as Therapeutic Targets in Sinonasal Intestinal-Type Adenocarcinoma Codina-Martínez, Helena Lorenzo-Guerra, Sara Lucila Cabal, Virginia N. García-Marín, Rocío Suárez-Fernández, Laura Vivanco, Blanca Sánchez-Fernández, Paula López, Fernando Llorente, José Luis Hermsen, Mario A. Int J Mol Sci Article Despite advances in surgery and radiotherapy, the overall prognosis of sinonasal intestinal-type adenocarcinoma (ITAC) is poor, and new treatment options are needed. Recent studies have indicated alterations in cellular signaling pathways that may serve as targets for modern inhibitors. Our aim was to evaluate the frequency of mTOR and ERK pathway upregulation in a retrospective series of 139 ITAC and to test the efficacy and mechanism of action of candidate targeted inhibitors in cell line ITAC-3. An immunohistochemical analysis on p-AKT, p-mTOR, p-S6, p-4E-BP1, and p-ERK indicated, respectively, a 68% and 57% mTOR and ERK pathway activation. In vitro studies using low doses of mTOR inhibitor everolimus and ERK inhibitor selumetinib showed significant growth inhibition as monotherapy and especially as combined therapy. This effect was accompanied by the downregulation of mTOR and ERK protein expression. Our data open a new and promising possibility for personalized treatment of ITAC patients. MDPI 2023-10-12 /pmc/articles/PMC10606341/ /pubmed/37894790 http://dx.doi.org/10.3390/ijms242015110 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Codina-Martínez, Helena
Lorenzo-Guerra, Sara Lucila
Cabal, Virginia N.
García-Marín, Rocío
Suárez-Fernández, Laura
Vivanco, Blanca
Sánchez-Fernández, Paula
López, Fernando
Llorente, José Luis
Hermsen, Mario A.
Signaling Pathways mTOR and ERK as Therapeutic Targets in Sinonasal Intestinal-Type Adenocarcinoma
title Signaling Pathways mTOR and ERK as Therapeutic Targets in Sinonasal Intestinal-Type Adenocarcinoma
title_full Signaling Pathways mTOR and ERK as Therapeutic Targets in Sinonasal Intestinal-Type Adenocarcinoma
title_fullStr Signaling Pathways mTOR and ERK as Therapeutic Targets in Sinonasal Intestinal-Type Adenocarcinoma
title_full_unstemmed Signaling Pathways mTOR and ERK as Therapeutic Targets in Sinonasal Intestinal-Type Adenocarcinoma
title_short Signaling Pathways mTOR and ERK as Therapeutic Targets in Sinonasal Intestinal-Type Adenocarcinoma
title_sort signaling pathways mtor and erk as therapeutic targets in sinonasal intestinal-type adenocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10606341/
https://www.ncbi.nlm.nih.gov/pubmed/37894790
http://dx.doi.org/10.3390/ijms242015110
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