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dc.contributor.author | Gonzalez-Cao, Maria![]() |
es_ES |
dc.contributor.author | Cai, Xueting![]() |
es_ES |
dc.contributor.author | Bracht, Jilian Wilhelmina Paulina![]() |
es_ES |
dc.contributor.author | Han, Xuan![]() |
es_ES |
dc.contributor.author | Yang, Yang![]() |
es_ES |
dc.contributor.author | Pedraz-Valdunciel, Carlos![]() |
es_ES |
dc.contributor.author | Morán, Teresa![]() |
es_ES |
dc.contributor.author | García-Corbacho, Javier![]() |
es_ES |
dc.contributor.author | Aguilar, Andrés![]() |
es_ES |
dc.contributor.author | Bernabé, Reyes![]() |
es_ES |
dc.contributor.author | De Marchi, Pedro![]() |
es_ES |
dc.contributor.author | da Silva, Luciane Sussuchi![]() |
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dc.contributor.author | Ferro Leal, Leticia![]() |
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dc.contributor.author | Reis, Rui Manuel![]() |
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dc.contributor.author | Codony-Servat, Jordi![]() |
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dc.contributor.author | Jantus-Lewintre, Eloisa![]() |
es_ES |
dc.date.accessioned | 2024-07-26T18:10:53Z | |
dc.date.available | 2024-07-26T18:10:53Z | |
dc.date.issued | 2024-05-09 | es_ES |
dc.identifier.uri | http://hdl.handle.net/10251/206712 | |
dc.description.abstract | [EN] Purpose: High-mobility group box 1 protein (HMGB1) is subject to exportin 1 (XPO1)-dependent nuclear export, and it is involved in functions implicated in resistance to immunotherapy. We investigated whether HMGB1 mRNA expression was associated with response to immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC). Patients and Methods: RNA was isolated from pretreatment biopsies of patients with advanced NSCLC treated with ICI. Gene expression analysis of several genes, including HMGB1, was conducted using the NanoString Counter analysis system (PanCancer Immune Profiling Panel). Western blotting analysis and cell viability assays in EGFR and KRAS mutant cell lines were carried out. Evaluation of the antitumoral effect of ICI in combination with XPO1 blocker (selinexor) and trametinib was determined in a murine Results: HMGB1 mRNA levels in NSCLC patients treated with ICI correlated with progression-free survival (PFS) (median PFS 9.0 versus 18.0 months, P=0.008, hazard ratio=0.30 in high versus low HMGB1). After TNF-alpha stimulation, HMGB1 accumulates in the cytoplasm of PC9 cells, but this accumulation can be prevented by using selinexor or antiretroviral drugs. Erlotinib or osimertinib with selinexor in EGFR-mutant cells and trametinib plus selinexor in KRAS mutant abolish tumor cell proliferation. Selinexor with a PD-1 inhibitor with or without trametinib abrogates the tumor growth in the murine Lewis lung cancer model. Conclusion: An in-depth exploration of the functions of HMGB1 mRNA and protein is expected to uncover new potential targets and provide a basis for treating metastatic NSCLC in combination with ICI. | es_ES |
dc.description.sponsorship | The investigators wish to thank the patients for kindly agreeing to donate samples to this study. We also thank all the physicians who collaborated by providing clinical information. This work was supported by a European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement ELBA [No 765492] , the National Science Foundation for Distinguished Young Scholars [82125037] , the Major National Science and Technology Program of China for Innovative Drug [2017ZX09101002-002-006] , and by the Key R&D Program of Jiangsu Province [BE2018755, HBZ2021-012] . This work was also partially supported by a Spanish Association Against Cancer (AECC) grant (PROYE18012ROSE) and by the Public Ministry of Labor Campinas (Research, Prevention, and Education of Occupational Cancer) . This work is in memory of the generous support provided by the late Julian Santamaria Valino to the IOR Foundation.r the Public Ministry of Labor Campinas (Research, Prevention, and Education of Occupational Cancer) . This work is in memory of the generous support provided by the late Julian Santamaria Valino to the IOR Foundation. | es_ES |
dc.language | Inglés | es_ES |
dc.relation.ispartof | LUNG CANCER-TARGETS AND THERAPY | es_ES |
dc.rights | Reconocimiento - No comercial (by-nc) | es_ES |
dc.subject | HMGB1 | es_ES |
dc.subject | K-Ras mutations | es_ES |
dc.subject | Lewis lung cancer murine model | es_ES |
dc.subject | Immunotherapy | es_ES |
dc.subject | Non-small cell lung cancer | es_ES |
dc.subject.classification | BIOLOGIA CELULAR | es_ES |
dc.title | HMGB1 Expression Levels Correlate with Response to Immunotherapy in Non-Small Cell Lung Cancer | es_ES |
dc.type | Artículo | es_ES |
dc.identifier.doi | 10.2147/LCTT.S455034 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/765492/EU/Towards widespread clinical application of blood- based diagnostic tools/ | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/AECC//PROYE18012ROSE/ | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/National Major Science and Technology Projects of China//2017ZX09101002-002-006/ | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/National Major Science and Technology Projects of China//HBZ2021-012/ | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/National Major Science and Technology Projects of China//BE2018755/ | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/National Science Fund for Distinguished Young Scholars//82125037/ | es_ES |
dc.rights.accessRights | Abierto | es_ES |
dc.contributor.affiliation | Universitat Politècnica de València. Escuela Técnica Superior de Ingeniería Agronómica y del Medio Natural - Escola Tècnica Superior d'Enginyeria Agronòmica i del Medi Natural | es_ES |
dc.description.bibliographicCitation | Gonzalez-Cao, M.; Cai, X.; Bracht, JWP.; Han, X.; Yang, Y.; Pedraz-Valdunciel, C.; Morán, T.... (2024). HMGB1 Expression Levels Correlate with Response to Immunotherapy in Non-Small Cell Lung Cancer. LUNG CANCER-TARGETS AND THERAPY. 15:55-67. https://doi.org/10.2147/LCTT.S455034 | es_ES |
dc.description.accrualMethod | S | es_ES |
dc.relation.publisherversion | https://doi.org/10.2147/LCTT.S455034 | es_ES |
dc.description.upvformatpinicio | 55 | es_ES |
dc.description.upvformatpfin | 67 | es_ES |
dc.type.version | info:eu-repo/semantics/publishedVersion | es_ES |
dc.description.volume | 15 | es_ES |
dc.identifier.eissn | 1179-2728 | es_ES |
dc.identifier.pmid | 38741920 | es_ES |
dc.identifier.pmcid | PMC11090191 | es_ES |
dc.relation.pasarela | S\520052 | es_ES |
dc.contributor.funder | European Commission | es_ES |
dc.contributor.funder | Universitat Politècnica de València | es_ES |
dc.contributor.funder | Asociación Española Contra el Cáncer | es_ES |
dc.contributor.funder | National Science Fund for Distinguished Young Scholars | es_ES |
dc.contributor.funder | National Major Science and Technology Projects of China | es_ES |