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mTOR Pathway Expression as Potential Predictive Biomarker in Patients with Advanced Neuroendocrine Tumors Treated with Everolimus

Background. Everolimus (Eve), which is a mammalian target of Rapamicin (mTOR) inhibitor, is part of the therapeutic armamentarium of neuroendocrine tumors (NETs). Currently, there are no validated biomarkers predicting Eve efficacy in NETs. In this study, we explore whether the expression of phospho...

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Autores principales: Gelsomino, Fabio, Casadei-Gardini, Andrea, Caputo, Francesco, Rossi, Giulio, Bertolini, Federica, Petrachi, Tiziana, Spallanzani, Andrea, Pettorelli, Elisa, Kaleci, Shaniko, Luppi, Gabriele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281483/
https://www.ncbi.nlm.nih.gov/pubmed/32397669
http://dx.doi.org/10.3390/cancers12051201
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author Gelsomino, Fabio
Casadei-Gardini, Andrea
Caputo, Francesco
Rossi, Giulio
Bertolini, Federica
Petrachi, Tiziana
Spallanzani, Andrea
Pettorelli, Elisa
Kaleci, Shaniko
Luppi, Gabriele
author_facet Gelsomino, Fabio
Casadei-Gardini, Andrea
Caputo, Francesco
Rossi, Giulio
Bertolini, Federica
Petrachi, Tiziana
Spallanzani, Andrea
Pettorelli, Elisa
Kaleci, Shaniko
Luppi, Gabriele
author_sort Gelsomino, Fabio
collection PubMed
description Background. Everolimus (Eve), which is a mammalian target of Rapamicin (mTOR) inhibitor, is part of the therapeutic armamentarium of neuroendocrine tumors (NETs). Currently, there are no validated biomarkers predicting Eve efficacy in NETs. In this study, we explore whether the expression of phosphorilated (p)-mTOR and p70S6-kinase (S6K), a downstream effector of mTOR, correlates with the outcome of patients with NET that were treated with Eve. Methods. Tissue specimens that were derived from NETs treated with Eve at our Institution were examined for the expression levels of p-mTOR and p-S6K by immunohistochemistry. Response rate (RR), progression-free survival (PFS), and overall survival (OS) were analyzed in two groups: p-mTOR/p-S6K positive (group 1) and p-mTOR/p-S6K negative (group 2). Univariate and multivariate Cox regression analysis were performed. Results. Twenty-four patients with advanced NETs that were treated with Eve were included in the analysis. Eight out 24 (33.3%) patients were both p-mTOR and p-S6K positive. A better median PFS and OS in group 1 (18.2 and 39.9 months) as compared to group 2 (13 and 32.4 months) was depicted, with a toxicity profile that was comparable with data literature. Conclusions. Our study suggests that the activation of mTOR pathway can predict better outcomes in patients with NET treated with Eve. However, these results warrant further confirmation in a prospective setting.
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spelling pubmed-72814832020-06-17 mTOR Pathway Expression as Potential Predictive Biomarker in Patients with Advanced Neuroendocrine Tumors Treated with Everolimus Gelsomino, Fabio Casadei-Gardini, Andrea Caputo, Francesco Rossi, Giulio Bertolini, Federica Petrachi, Tiziana Spallanzani, Andrea Pettorelli, Elisa Kaleci, Shaniko Luppi, Gabriele Cancers (Basel) Article Background. Everolimus (Eve), which is a mammalian target of Rapamicin (mTOR) inhibitor, is part of the therapeutic armamentarium of neuroendocrine tumors (NETs). Currently, there are no validated biomarkers predicting Eve efficacy in NETs. In this study, we explore whether the expression of phosphorilated (p)-mTOR and p70S6-kinase (S6K), a downstream effector of mTOR, correlates with the outcome of patients with NET that were treated with Eve. Methods. Tissue specimens that were derived from NETs treated with Eve at our Institution were examined for the expression levels of p-mTOR and p-S6K by immunohistochemistry. Response rate (RR), progression-free survival (PFS), and overall survival (OS) were analyzed in two groups: p-mTOR/p-S6K positive (group 1) and p-mTOR/p-S6K negative (group 2). Univariate and multivariate Cox regression analysis were performed. Results. Twenty-four patients with advanced NETs that were treated with Eve were included in the analysis. Eight out 24 (33.3%) patients were both p-mTOR and p-S6K positive. A better median PFS and OS in group 1 (18.2 and 39.9 months) as compared to group 2 (13 and 32.4 months) was depicted, with a toxicity profile that was comparable with data literature. Conclusions. Our study suggests that the activation of mTOR pathway can predict better outcomes in patients with NET treated with Eve. However, these results warrant further confirmation in a prospective setting. MDPI 2020-05-10 /pmc/articles/PMC7281483/ /pubmed/32397669 http://dx.doi.org/10.3390/cancers12051201 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gelsomino, Fabio
Casadei-Gardini, Andrea
Caputo, Francesco
Rossi, Giulio
Bertolini, Federica
Petrachi, Tiziana
Spallanzani, Andrea
Pettorelli, Elisa
Kaleci, Shaniko
Luppi, Gabriele
mTOR Pathway Expression as Potential Predictive Biomarker in Patients with Advanced Neuroendocrine Tumors Treated with Everolimus
title mTOR Pathway Expression as Potential Predictive Biomarker in Patients with Advanced Neuroendocrine Tumors Treated with Everolimus
title_full mTOR Pathway Expression as Potential Predictive Biomarker in Patients with Advanced Neuroendocrine Tumors Treated with Everolimus
title_fullStr mTOR Pathway Expression as Potential Predictive Biomarker in Patients with Advanced Neuroendocrine Tumors Treated with Everolimus
title_full_unstemmed mTOR Pathway Expression as Potential Predictive Biomarker in Patients with Advanced Neuroendocrine Tumors Treated with Everolimus
title_short mTOR Pathway Expression as Potential Predictive Biomarker in Patients with Advanced Neuroendocrine Tumors Treated with Everolimus
title_sort mtor pathway expression as potential predictive biomarker in patients with advanced neuroendocrine tumors treated with everolimus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281483/
https://www.ncbi.nlm.nih.gov/pubmed/32397669
http://dx.doi.org/10.3390/cancers12051201
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