2026-05-21T23:03:28Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/253002025-12-18T12:59:52Zcom_20.500.12105_2327com_20.500.12105_2290col_20.500.12105_16991
Repisalud author Monteiro, Cátia author Miarka, Lauritz author Perea-García, María author Priego, Neibla author García-Gómez, Pedro author Álvaro-Espinosa, Laura author de Pablos-Aragoneses, Ana author Yebra, Natalia author Retana, Diana author Baena, Patricia author Fustero-Torre, Coral author Graña-Castro, Osvaldo author Troulé, Kevin author Caleiras, Eduardo author Tezanos, Patricia author Muela, Pablo author Cintado, Elisa author Trejo, José Luis author Sepúlveda, Juan Manuel author González-León, Pedro author Jiménez-Roldán, Luis author Moreno, Luis Miguel author Esteban, Olga author Pérez-Núñez, Ángel author Hernández-Laín, Aurelio author Mazarico Gallego, José author Ferrer, Irene author Suárez, Rocío author Garrido-Martín, Eva M author Paz-Ares, Luis author Dalmasso, Celine author Cohen-Jonathan Moyal, Elizabeth author Siegfried, Aurore author Hegarty, Aisling author Keelan, Stephen author Varešlija, Damir author Young, Leonie S author Mohme, Malte author Goy, Yvonne author Wikman, Harriet author Fernández-Alén, Jose author Blasco, Guillermo author Alcázar, Lucía author Cabañuz, Clara author Grivennikov, Sergei I author Ianus, Andrada author Shemesh, Noam author Faria, Claudia C author Lee, Rebecca author Lorigan, Paul author Le Rhun, Emilie author Weller, Michael author Soffietti, Riccardo author Bertero, Luca author Ricardi, Umberto author Bosch-Barrera, Joaquim author Sais, Elia author Teixidor, Eduard author Hernández-Martínez, Alejandro author Calvo, Alfonso author Aristu, Javier author Martin, Santiago M author Gonzalez, Alvaro author Adler, Omer author Erez, Neta author Valiente, Manuel author Monteiro, Cátia author Miarka, Lauritz author Perea-García, María author Priego, Neibla author García-Gómez, Pedro author Álvaro-Espinosa, Laura author de Pablos-Aragoneses, Ana author Yebra, Natalia author Retana, Diana author Baena, Patricia author Fustero-Torre, Coral author Graña-Castro, Osvaldo author Troulé, Kevin author Caleiras, Eduardo author Tezanos, Patricia author Muela, Pablo author Cintado, Elisa author Trejo, José Luis author Sepúlveda, Juan Manuel author González-León, Pedro author Jiménez-Roldán, Luis author Moreno, Luis Miguel author Esteban, Olga author Pérez-Núñez, Ángel author Hernández-Lain, Aurelio author Mazarico Gallego, José author Ferrer, Irene author Suárez, Rocío author Garrido-Martín, Eva M author Paz-Ares, Luis author Dalmasso, Celine author Cohen-Jonathan Moyal, Elizabeth author Siegfried, Aurore author Hegarty, Aisling author Keelan, Stephen author Varešlija, Damir author Young, Leonie S author Mohme, Malte author Goy, Yvonne author Wikman, Harriet author Fernández-Alén, Jose author Blasco, Guillermo author Alcázar, Lucía author Cabañuz, Clara author Grivennikov, Sergei I author Ianus, Andrada author Shemesh, Noam author Faria, Claudia C author Lee, Rebecca author Lorigan, Paul author Le Rhun, Emilie author Weller, Michael author Soffietti, Riccardo author Bertero, Luca author Ricardi, Umberto author Bosch-Barrera, Joaquim author Sais, Elia author Teixidor, Eduard author Hernández-Martínez, Alejandro author Calvo, Alfonso author Aristu, Javier author Martin, Santiago M author Gonzalez, Alvaro author Adler, Omer author Erez, Neta funder Fundación La Marató TV3 funder Fundación Ramón Areces funder Worldwide Cancer Research funder Asociación Española Contra el Cáncer funder Ministerio de Ciencia e Innovación (España) funder Unión Europea. Comisión Europea. European Research Council (ERC) funder Science Foundation Ireland funder Fundación La Caixa funder Unión Europea. Comisión Europea. H2020 funder NIH - National Cancer Institute (NCI) (Estados Unidos) 2024-10-25T11:41:56Z 2024-10-25T11:41:56Z 2022-04 Nat Med . 2022 Apr;28(4):752-765. Nature Medicine 35411077 https://hdl.handle.net/20.500.12105/25300 Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity. eng SET ENRICHMENT ANALYSIS GLYCATION END-PRODUCTS STEREOTACTIC RADIOSURGERY RADIATION-THERAPY MOUSE-BRAIN CANCER CELL RAGE RADIOTHERAPY RECEPTOR Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism. research article 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 URL https://repisalud.isciii.es/bitstreams/dfba491f-59d4-4467-82c0-2dcf480cb4cc/download File MD5 242bf1aedf785b501e03c9ede8e6413e 11414435 application/pdf Stratificationofradiosensitivebrain-2022.pdf URL https://repisalud.isciii.es/bitstreams/4cb12912-aafe-4946-b882-039e8b7d73f8/download File MD5 5e1c253f3851cd25b82abfcc35bb70c2 101177 text/plain Stratificationofradiosensitivebrain-2022.pdf.txt