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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| Format: | Article |
| Language: | English |
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MDPI AG
2021-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/5/2538 |
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| author | Ángela Marrugal Irene Ferrer David Gómez-Sánchez Álvaro Quintanal-Villalonga María Dolores Pastor Laura Ojeda Luis Paz-Ares Sonia Molina-Pinelo |
| author_facet | Ángela Marrugal Irene Ferrer David Gómez-Sánchez Álvaro Quintanal-Villalonga María Dolores Pastor Laura Ojeda Luis Paz-Ares Sonia Molina-Pinelo |
| author_sort | Ángela Marrugal |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T05:43:41Z |
| format | Article |
| id | doaj.art-ecbb2dceb7b14048942b2b6536dc3ea6 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:43:41Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ecbb2dceb7b14048942b2b6536dc3ea62023-12-03T12:23:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01225253810.3390/ijms22052538Identification of Predictive Biomarkers of Response to HSP90 Inhibitors in Lung AdenocarcinomaÁngela Marrugal0Irene Ferrer1David Gómez-Sánchez2Álvaro Quintanal-Villalonga3María Dolores Pastor4Laura Ojeda5Luis Paz-Ares6Sonia Molina-Pinelo7H12O-CNIO Lung Cancer Clinical Research Unit, Instituto de Investigación Hospital 12 de Octubre & Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, SpainH12O-CNIO Lung Cancer Clinical Research Unit, Instituto de Investigación Hospital 12 de Octubre & Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, SpainH12O-CNIO Lung Cancer Clinical Research Unit, Instituto de Investigación Hospital 12 de Octubre & Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, SpainProgram in Molecular Pharmacology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USAInstitute of Biomedicine of Seville (IBIS) (HUVR, CSIC, Universidad de Sevilla), 41013 Sevilla, SpainH12O-CNIO Lung Cancer Clinical Research Unit, Instituto de Investigación Hospital 12 de Octubre & Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, SpainH12O-CNIO Lung Cancer Clinical Research Unit, Instituto de Investigación Hospital 12 de Octubre & Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, SpainCIBERONC, Respiratory Tract Tumors Program, 28029 Madrid, SpainHeat 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.https://www.mdpi.com/1422-0067/22/5/2538HSP90 inhibitorsprotein biomarkers predictive of responselung adenocarcinoma |
| spellingShingle | Ángela Marrugal Irene Ferrer David Gómez-Sánchez Álvaro Quintanal-Villalonga María Dolores Pastor Laura Ojeda Luis Paz-Ares Sonia Molina-Pinelo Identification of Predictive Biomarkers of Response to HSP90 Inhibitors in Lung Adenocarcinoma International Journal of Molecular Sciences HSP90 inhibitors protein biomarkers predictive of response 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 | HSP90 inhibitors protein biomarkers predictive of response lung adenocarcinoma |
| url | https://www.mdpi.com/1422-0067/22/5/2538 |
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