Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism

Detalhes bibliográficos
Autor(a) principal: Monteiro, Cátia
Data de Publicação: 2022
Outros Autores: Miarka, Lauritz, Perea-García, María, Priego, Neibla, García-Gómez, Pedro, Álvaro-Espinosa, Laura, de Pablos-Aragoneses, Ana, Yebra, Natalia, Retana, Diana, Baena, Patricia, Fustero-Torre, Coral, Graña-Castro, Osvaldo, Troulé, Kevin, Caleiras, Eduardo, Tezanos, Patricia, Muela, Pablo, Cintado, Elisa, Trejo, José Luis, Sepúlveda, Juan Manuel, González-León, Pedro, Jiménez-Roldán, Luis, Moreno, Luis Miguel, Esteban, Olga, Pérez-Núñez, Ángel, Hernández-Lain, Aurelio, Mazarico Gallego, José, Ferrer, Irene, Suárez, Rocío, Garrido-Martín, Eva M., Paz-Ares, Luis, Dalmasso, Celine, Cohen-Jonathan Moyal, Elizabeth, Siegfried, Aurore, Hegarty, Aisling, Keelan, Stephen, Varešlija, Damir, Young, Leonie S., Mohme, Malte, Goy, Yvonne, Wikman, Harriet, Fernández-Alén, Jose, Blasco, Guillermo, Alcázar, Lucía, Cabañuz, Clara, Grivennikov, Sergei I., Ianus, Andrada, Shemesh, Noam, Faria, Claudia, Lee, Rebecca, Lorigan, Paul, Le Rhun, Emilie, Weller, Michael, Soffietti, Riccardo, Bertero, Luca, Ricardi, Umberto, Bosch-Barrera, Joaquim, Sais, Elia, Teixidor, Eduard, Hernández-Martínez, Alejandro, Calvo, Alfonso, Aristu, Javier, Martin, Santiago M., Gonzalez, Alvaro, Adler, Omer, Erez, Neta, Sobrino, Cecilia, Ajenjo, Nuria, Artiga, Maria-Jesus, Ortega-Paino, Eva, Valiente, Manuel
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/52536
Resumo: © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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spelling Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.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.Springer NatureRepositório da Universidade de LisboaMonteiro, CátiaMiarka, LauritzPerea-García, MaríaPriego, NeiblaGarcía-Gómez, PedroÁlvaro-Espinosa, Laurade Pablos-Aragoneses, AnaYebra, NataliaRetana, DianaBaena, PatriciaFustero-Torre, CoralGraña-Castro, OsvaldoTroulé, KevinCaleiras, EduardoTezanos, PatriciaMuela, PabloCintado, ElisaTrejo, José LuisSepúlveda, Juan ManuelGonzález-León, PedroJiménez-Roldán, LuisMoreno, Luis MiguelEsteban, OlgaPérez-Núñez, ÁngelHernández-Lain, AurelioMazarico Gallego, JoséFerrer, IreneSuárez, RocíoGarrido-Martín, Eva M.Paz-Ares, LuisDalmasso, CelineCohen-Jonathan Moyal, ElizabethSiegfried, AuroreHegarty, AislingKeelan, StephenVarešlija, DamirYoung, Leonie S.Mohme, MalteGoy, YvonneWikman, HarrietFernández-Alén, JoseBlasco, GuillermoAlcázar, LucíaCabañuz, ClaraGrivennikov, Sergei I.Ianus, AndradaShemesh, NoamFaria, ClaudiaLee, RebeccaLorigan, PaulLe Rhun, EmilieWeller, MichaelSoffietti, RiccardoBertero, LucaRicardi, UmbertoBosch-Barrera, JoaquimSais, EliaTeixidor, EduardHernández-Martínez, AlejandroCalvo, AlfonsoAristu, JavierMartin, Santiago M.Gonzalez, AlvaroAdler, OmerErez, NetaSobrino, CeciliaAjenjo, NuriaArtiga, Maria-JesusOrtega-Paino, EvaValiente, Manuel2022-04-22T16:55:21Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/52536engNat Med. 2022 Apr;28(4):752-7651078-895610.1038/s41591-022-01749-81546-170Xinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:57:47Zoai:repositorio.ul.pt:10451/52536Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:03:37.511597Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism
title Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism
spellingShingle Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism
Monteiro, Cátia
title_short Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism
title_full Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism
title_fullStr Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism
title_full_unstemmed Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism
title_sort Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism
author Monteiro, Cátia
author_facet Monteiro, Cátia
Miarka, Lauritz
Perea-García, María
Priego, Neibla
García-Gómez, Pedro
Álvaro-Espinosa, Laura
de Pablos-Aragoneses, Ana
Yebra, Natalia
Retana, Diana
Baena, Patricia
Fustero-Torre, Coral
Graña-Castro, Osvaldo
Troulé, Kevin
Caleiras, Eduardo
Tezanos, Patricia
Muela, Pablo
Cintado, Elisa
Trejo, José Luis
Sepúlveda, Juan Manuel
González-León, Pedro
Jiménez-Roldán, Luis
Moreno, Luis Miguel
Esteban, Olga
Pérez-Núñez, Ángel
Hernández-Lain, Aurelio
Mazarico Gallego, José
Ferrer, Irene
Suárez, Rocío
Garrido-Martín, Eva M.
Paz-Ares, Luis
Dalmasso, Celine
Cohen-Jonathan Moyal, Elizabeth
Siegfried, Aurore
Hegarty, Aisling
Keelan, Stephen
Varešlija, Damir
Young, Leonie S.
Mohme, Malte
Goy, Yvonne
Wikman, Harriet
Fernández-Alén, Jose
Blasco, Guillermo
Alcázar, Lucía
Cabañuz, Clara
Grivennikov, Sergei I.
Ianus, Andrada
Shemesh, Noam
Faria, Claudia
Lee, Rebecca
Lorigan, Paul
Le Rhun, Emilie
Weller, Michael
Soffietti, Riccardo
Bertero, Luca
Ricardi, Umberto
Bosch-Barrera, Joaquim
Sais, Elia
Teixidor, Eduard
Hernández-Martínez, Alejandro
Calvo, Alfonso
Aristu, Javier
Martin, Santiago M.
Gonzalez, Alvaro
Adler, Omer
Erez, Neta
Sobrino, Cecilia
Ajenjo, Nuria
Artiga, Maria-Jesus
Ortega-Paino, Eva
Valiente, Manuel
author_role author
author2 Miarka, Lauritz
Perea-García, María
Priego, Neibla
García-Gómez, Pedro
Álvaro-Espinosa, Laura
de Pablos-Aragoneses, Ana
Yebra, Natalia
Retana, Diana
Baena, Patricia
Fustero-Torre, Coral
Graña-Castro, Osvaldo
Troulé, Kevin
Caleiras, Eduardo
Tezanos, Patricia
Muela, Pablo
Cintado, Elisa
Trejo, José Luis
Sepúlveda, Juan Manuel
González-León, Pedro
Jiménez-Roldán, Luis
Moreno, Luis Miguel
Esteban, Olga
Pérez-Núñez, Ángel
Hernández-Lain, Aurelio
Mazarico Gallego, José
Ferrer, Irene
Suárez, Rocío
Garrido-Martín, Eva M.
Paz-Ares, Luis
Dalmasso, Celine
Cohen-Jonathan Moyal, Elizabeth
Siegfried, Aurore
Hegarty, Aisling
Keelan, Stephen
Varešlija, Damir
Young, Leonie S.
Mohme, Malte
Goy, Yvonne
Wikman, Harriet
Fernández-Alén, Jose
Blasco, Guillermo
Alcázar, Lucía
Cabañuz, Clara
Grivennikov, Sergei I.
Ianus, Andrada
Shemesh, Noam
Faria, Claudia
Lee, Rebecca
Lorigan, Paul
Le Rhun, Emilie
Weller, Michael
Soffietti, Riccardo
Bertero, Luca
Ricardi, Umberto
Bosch-Barrera, Joaquim
Sais, Elia
Teixidor, Eduard
Hernández-Martínez, Alejandro
Calvo, Alfonso
Aristu, Javier
Martin, Santiago M.
Gonzalez, Alvaro
Adler, Omer
Erez, Neta
Sobrino, Cecilia
Ajenjo, Nuria
Artiga, Maria-Jesus
Ortega-Paino, Eva
Valiente, Manuel
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dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Monteiro, Cátia
Miarka, Lauritz
Perea-García, María
Priego, Neibla
García-Gómez, Pedro
Álvaro-Espinosa, Laura
de Pablos-Aragoneses, Ana
Yebra, Natalia
Retana, Diana
Baena, Patricia
Fustero-Torre, Coral
Graña-Castro, Osvaldo
Troulé, Kevin
Caleiras, Eduardo
Tezanos, Patricia
Muela, Pablo
Cintado, Elisa
Trejo, José Luis
Sepúlveda, Juan Manuel
González-León, Pedro
Jiménez-Roldán, Luis
Moreno, Luis Miguel
Esteban, Olga
Pérez-Núñez, Ángel
Hernández-Lain, Aurelio
Mazarico Gallego, José
Ferrer, Irene
Suárez, Rocío
Garrido-Martín, Eva M.
Paz-Ares, Luis
Dalmasso, Celine
Cohen-Jonathan Moyal, Elizabeth
Siegfried, Aurore
Hegarty, Aisling
Keelan, Stephen
Varešlija, Damir
Young, Leonie S.
Mohme, Malte
Goy, Yvonne
Wikman, Harriet
Fernández-Alén, Jose
Blasco, Guillermo
Alcázar, Lucía
Cabañuz, Clara
Grivennikov, Sergei I.
Ianus, Andrada
Shemesh, Noam
Faria, Claudia
Lee, Rebecca
Lorigan, Paul
Le Rhun, Emilie
Weller, Michael
Soffietti, Riccardo
Bertero, Luca
Ricardi, Umberto
Bosch-Barrera, Joaquim
Sais, Elia
Teixidor, Eduard
Hernández-Martínez, Alejandro
Calvo, Alfonso
Aristu, Javier
Martin, Santiago M.
Gonzalez, Alvaro
Adler, Omer
Erez, Neta
Sobrino, Cecilia
Ajenjo, Nuria
Artiga, Maria-Jesus
Ortega-Paino, Eva
Valiente, Manuel
description © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
publishDate 2022
dc.date.none.fl_str_mv 2022-04-22T16:55:21Z
2022
2022-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/52536
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dc.relation.none.fl_str_mv Nat Med. 2022 Apr;28(4):752-765
1078-8956
10.1038/s41591-022-01749-8
1546-170X
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