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Identification of Predictive Biomarkers of Response to HSP90 Inhibitors in Lung Adenocarcinoma

Heat shock protein 90 (HSP90) plays an essential role in lung adenocarcinoma, acting as a key chaperone involved in the correct functioning of numerous highly relevant protein drivers of this disease. To this end, HSP90 inhibitors have emerged as promising therapeutic strategies, even though respons...

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Autores principales: Marrugal, Ángela, Ferrer, Irene, Gómez-Sánchez, David, Quintanal-Villalonga, Álvaro, Pastor, María Dolores, Ojeda, Laura, Paz-Ares, Luis, Molina-Pinelo, Sonia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962034/
https://www.ncbi.nlm.nih.gov/pubmed/33802597
http://dx.doi.org/10.3390/ijms22052538
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author Marrugal, Ángela
Ferrer, Irene
Gómez-Sánchez, David
Quintanal-Villalonga, Álvaro
Pastor, María Dolores
Ojeda, Laura
Paz-Ares, Luis
Molina-Pinelo, Sonia
author_facet Marrugal, Ángela
Ferrer, Irene
Gómez-Sánchez, David
Quintanal-Villalonga, Álvaro
Pastor, María Dolores
Ojeda, Laura
Paz-Ares, Luis
Molina-Pinelo, Sonia
author_sort Marrugal, Ángela
collection PubMed
description Heat shock protein 90 (HSP90) plays an essential role in lung adenocarcinoma, acting as a key chaperone involved in the correct functioning of numerous highly relevant protein drivers of this disease. To this end, HSP90 inhibitors have emerged as promising therapeutic strategies, even though responses to them have been limited to date. Given the need to maximize treatment efficacy, the objective of this study was to use isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic techniques to identify proteins in human lung adenocarcinoma cell lines whose basal abundances were correlated with response to HSP90 inhibitors (geldanamycin and radicicol derivatives). From the protein profiles identified according to response, the relationship between lactate dehydrogenase B (LDHB) and DNA topoisomerase 1 (TOP1) with respect to sensitivity and resistance, respectively, to geldanamycin derivatives is noteworthy. Likewise, rhotekin (RTKN) and decaprenyl diphosphate synthase subunit 2 (PDSS2) were correlated with sensitivity and resistance to radicicol derivatives. We also identified a relationship between resistance to HSP90 inhibition and the p53 pathway by glucose deprivation. In contrast, arginine biosynthesis was correlated with sensitivity to HSP90 inhibitors. Further study of these outcomes could enable the development of strategies to improve the clinical efficacy of HSP90 inhibition in patients with lung adenocarcinoma.
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spelling pubmed-79620342021-03-17 Identification of Predictive Biomarkers of Response to HSP90 Inhibitors in Lung Adenocarcinoma Marrugal, Ángela Ferrer, Irene Gómez-Sánchez, David Quintanal-Villalonga, Álvaro Pastor, María Dolores Ojeda, Laura Paz-Ares, Luis Molina-Pinelo, Sonia Int J Mol Sci Article Heat shock protein 90 (HSP90) plays an essential role in lung adenocarcinoma, acting as a key chaperone involved in the correct functioning of numerous highly relevant protein drivers of this disease. To this end, HSP90 inhibitors have emerged as promising therapeutic strategies, even though responses to them have been limited to date. Given the need to maximize treatment efficacy, the objective of this study was to use isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic techniques to identify proteins in human lung adenocarcinoma cell lines whose basal abundances were correlated with response to HSP90 inhibitors (geldanamycin and radicicol derivatives). From the protein profiles identified according to response, the relationship between lactate dehydrogenase B (LDHB) and DNA topoisomerase 1 (TOP1) with respect to sensitivity and resistance, respectively, to geldanamycin derivatives is noteworthy. Likewise, rhotekin (RTKN) and decaprenyl diphosphate synthase subunit 2 (PDSS2) were correlated with sensitivity and resistance to radicicol derivatives. We also identified a relationship between resistance to HSP90 inhibition and the p53 pathway by glucose deprivation. In contrast, arginine biosynthesis was correlated with sensitivity to HSP90 inhibitors. Further study of these outcomes could enable the development of strategies to improve the clinical efficacy of HSP90 inhibition in patients with lung adenocarcinoma. MDPI 2021-03-03 /pmc/articles/PMC7962034/ /pubmed/33802597 http://dx.doi.org/10.3390/ijms22052538 Text en © 2021 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
Marrugal, Ángela
Ferrer, Irene
Gómez-Sánchez, David
Quintanal-Villalonga, Álvaro
Pastor, María Dolores
Ojeda, Laura
Paz-Ares, Luis
Molina-Pinelo, Sonia
Identification of Predictive Biomarkers of Response to HSP90 Inhibitors in Lung Adenocarcinoma
title Identification of Predictive Biomarkers of Response to HSP90 Inhibitors in Lung Adenocarcinoma
title_full Identification of Predictive Biomarkers of Response to HSP90 Inhibitors in Lung Adenocarcinoma
title_fullStr Identification of Predictive Biomarkers of Response to HSP90 Inhibitors in Lung Adenocarcinoma
title_full_unstemmed Identification of Predictive Biomarkers of Response to HSP90 Inhibitors in Lung Adenocarcinoma
title_short Identification of Predictive Biomarkers of Response to HSP90 Inhibitors in Lung Adenocarcinoma
title_sort identification of predictive biomarkers of response to hsp90 inhibitors in lung adenocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962034/
https://www.ncbi.nlm.nih.gov/pubmed/33802597
http://dx.doi.org/10.3390/ijms22052538
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