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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-7962034 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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