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



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Marrugal, Ángela and Ferrer, Irene and Gómez Sánchez, David and Quintanal Villalonga, Álvaro and Pastor, María Dolores and Ojeda, Laura and Paz-Ares Rodríguez, Luis and Molina Pinelo, Sonia (2021) Identification of Predictive Biomarkers of Response to HSP90 Inhibitors in Lung Adenocarcinoma. International Journal of Molecular Sciences, 22 (5). p. 2538. ISSN 1422-0067

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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.

Item Type:Article
Uncontrolled Keywords:HSP90 inhibitors; protein biomarkers predictive of response; lung adenocarcinoma
Subjects:Medical sciences > Medicine > Biochemistry
Medical sciences > Medicine > Pneumology
Medical sciences > Medicine > Oncology
ID Code:71669
Deposited On:19 Apr 2022 15:11
Last Modified:20 Apr 2022 07:41

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