2026-06-28T14:59:03Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1060042025-03-18T15:46:40Zcom_20.500.14352_14col_20.500.14352_15

Docta Complutense author Marrugal, Ángela author Ferrer, Irene author Quintanal Villalonga, Álvaro author Ojeda Márquez, Laura author Pastor, María Dolores author García Luján, Ricardo author Carnero, Amancio author Paz-Ares Rodríguez, Luis Gonzaga author Molina Pinelo, Sonia 2024-07-12T07:17:19Z 2024-07-12T07:17:19Z 2023-09-07 Marrugal, Á.; Ferrer, I.; Quintanal-Villalonga, Á.; Ojeda, L.; Pastor, M.D.; García-Luján, R.; Carnero, A.; Paz-Ares, L.; Molina-Pinelo, S. Inhibition of HSP90 in Driver Oncogene-Defined Lung Adenocarcinoma Cell Lines: Key Proteins Underpinning Therapeutic Efficacy. Int. J. Mol. Sci. 2023, 24, 13830. https://doi.org/10.3390/ijms241813830 1422-0067 10.3390/ijms241813830 https://hdl.handle.net/20.500.14352/106004 https://doi.org/10.3390/ijms241813830 The use of 90 kDa heat shock protein (HSP90) inhibition as a therapy in lung adenocarcinoma remains limited due to moderate drug efficacy, the emergence of drug resistance, and early tumor recurrence. The main objective of this research is to maximize treatment efficacy in lung adenocarcinoma by identifying key proteins underlying HSP90 inhibition according to molecular background, and to search for potential biomarkers of response to this therapeutic strategy. Inhibition of the HSP90 chaperone was evaluated in different lung adenocarcinoma cell lines representing the most relevant molecular alterations (EGFR mutations, KRAS mutations, or EML4-ALK translocation) and wild-type genes found in each tumor subtype. The proteomic technique iTRAQ was used to identify proteomic profiles and determine which biological pathways are involved in the response to HSP90 inhibition in lung adenocarcinoma. We corroborated the greater efficacy of HSP90 inhibition in EGFR mutated or EML4-ALK translocated cell lines. We identified proteins specifically and significantly deregulated after HSP90 inhibition for each molecular alteration. Two proteins, ADI1 and RRP1, showed independently deregulated molecular patterns. Functional annotation of the altered proteins suggested that apoptosis was the only pathway affected by HSP90 inhibition across all molecular subgroups. The expression of ADI1 and RRP1 could be used to monitor the correct inhibition of HSP90 in lung adenocarcinoma. In addition, proteins such as ASS1, ITCH, or UBE2L3 involved in pathways related to the inhibition of a particular molecular background could be used as potential response biomarkers, thereby improving the efficacy of this therapeutic approach to combat lung adenocarcinoma. eng Attribution 4.0 International Inhibition of HSP90 in Driver Oncogene-Defined Lung Adenocarcinoma Cell Lines: Key Proteins Underpinning Therapeutic Efficacy journal article 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URL https://docta.ucm.es/bitstreams/3a7567a4-4af5-4cd4-854a-3c7ca18cae4e/download File MD5 5735e92e1bac70f1a365ab58425ccfc9 3802106 application/pdf Inhibition of HSP90 in Driver Oncogene.pdf URL https://docta.ucm.es/bitstreams/9534b94b-0a27-4709-bf14-2cbed2408c21/download File MD5 032b50bbc81d516a51ac9bcd6eb4051e 99352 text/plain Inhibition of HSP90 in Driver Oncogene.pdf.txt