2026-05-22T01:39:29Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/252992025-12-18T12:59:49Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud author Zhu, Lucía author Retana, Diana author García-Gómez, Pedro author Álvaro-Espinosa, Laura author Priego, Neibla author Masmudi-Martín, Mariam author Yebra, Natalia author Miarka, Lauritz author Hernández-Encinas, Elena author Blanco-Aparicio, Carmen author Martínez, Sonia author Sobrino, Cecilia author Ajenjo, Nuria author Artiga, Maria-Jesus author Ortega-Paino, Eva author Torres-Ruiz, Raúl author Rodríguez-Perales, Sandra author Soffietti, Riccardo author Bertero, Luca author Cassoni, Paola author Weiss, Tobias author Muñoz, Javier 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 Toldos, Oscar author Ruano, Yolanda author Alcázar, Lucía author Blasco, Guillermo author Fernández-Alén, José author Caleiras, Eduardo author Lafarga, Miguel author Megías, Diego author Graña-Castro, Osvaldo author Nör, Carolina author Taylor, Michael D author Young, Leonie S author Varešlija, Damir author Cosgrove, Nicola author Couch, Fergus J author Cussó, Lorena author Desco, Manuel author Mouron, Silvana author Quintela Fandino, Miguel Angel author Weller, Michael author Pastor Fernandez, Joaquin author Valiente, Manuel author Zhu, Lucía author Retana, Diana author García-Gómez, Pedro author Álvaro-Espinosa, Laura author Priego, Neibla author Masmudi-Martín, Mariam author Yebra, Natalia author Miarka, Lauritz author Hernández-Encinas, Elena author Blanco-Aparicio, Carmen author Martínez, Sonia author Sobrino, Cecilia author Ajenjo, Nuria author Artiga, Maria-Jesus author Ortega-Paino, Eva author Torres-Ruiz, Raúl author Rodríguez-Perales, Sandra author Soffietti, Riccardo author Bertero, Luca author Cassoni, Paola author Weiss, Tobias author Muñoz, Javier 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 Toldos, Oscar author Ruano, Yolanda author Alcázar, Lucía author Blasco, Guillermo author Fernández-Alén, José author Caleiras, Eduardo author Lafarga, Miguel author Megías, Diego author Graña-Castro, Osvaldo author Nör, Carolina author Taylor, Michael D author Young, Leonie S author Varešlija, Damir author Cosgrove, Nicola author Couch, Fergus J author Cussó, Lorena author Desco, Manuel author Mouron, Silvana author Weller, Michael funder Ministerio de Ciencia e Innovación (España) funder Fundación Fero funder Fundacio La Marato de TV3 funder NIHR - Bristol Biomedical Research Centre (Reino Unido) funder Fundacion Ramon Areces funder Worldwide Cancer Research funder Unión Europea. Comisión Europea. H2020 funder Asociación Española Contra el Cáncer funder Unión Europea. Comisión Europea. European Research Council (ERC) funder Instituto de Salud Carlos III funder Science Foundation Ireland funder Fundación La Caixa funder Fundación ProCNIC 2024-10-25T11:23:59Z 2024-10-25T11:23:59Z 2022-03-07 EMBO Mol Med . 2022 Mar 7;14(3):e14552. Embo Molecular Medicine 35174975 https://hdl.handle.net/20.500.12105/25299 We report a medium-throughput drug-screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood-brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastasis, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug-screening and unbiased omic approaches that is compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere. eng drug-screen metastasis organotypic cultures patient-derived resistance A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis. research article QWNlcHRhbmRvIGVzdGEgbGljZW5jaWEsIFVzdGVkIChlbCBhdXRvci9lcyBvIGVsIHByb3BpZXRhcmlvL3MgZGUgbG9zIGRlcmVjaG9zIGRlIGF1dG9yKSBjb25jZWRlIGEgUkVQSVNBTFVEIGVsIGRlcmVjaG8gbm8gZXhjbHVzaXZvIGRlIHJlcHJvZHVjaXIsIGNvbnZlcnRpciwgeS9vIGRpc3RyaWJ1aXIgc3UgZG9jdW1lbnRvIChpbmNsdXllbmRvIHN1IHJlc3VtZW4pIGEgbml2ZWwgbXVuZGlhbCBlbiBmb3JtYXRvIGRpZ2l0YWwsIGluY2x1eWVuZG8sIGF1ZGlvIHkgdsOtZGVvLCBhIHRyYXbDqXMgZGUgc3UgcmVwb3NpdG9yaW8gaW5zdGl0dWNpb25hbC4KClVzdGVkIGFjZXB0YSBxdWUgUkVQSVNBTFVEIHB1ZWRlLCBzaW4gYWx0ZXJhciBzdSBjb250ZW5pZG8sIGNvbnZlcnRpciBzdSBkb2N1bWVudG8gYSBjdWFscXVpZXIgb3RybyBmb3JtYXRvIGRpZ2l0YWwgZGUgZGF0b3MsIGF1ZGlvIHkgdmlkZW8sIGNvbiBlbCBwcm9ww7NzaXRvIGRlIHF1ZSBwdWVkYSBzZXIgYWxvamFkbyBlbiBlbCByZXBvc2l0b3Jpby4KClVzdGVkIGVzdMOhIGRlIGFjdWVyZG8gY29uIHF1ZSBSRVBJU0FMVUQgcHVlZGEgY29uc2VydmFyIG3DoXMgZGUgdW5hIGNvcGlhIGRlIGVzdGUgZG9jdW1lbnRvIHBhcmEgYXNlZ3VyYXIgc3Ugc2VndXJpZGFkLCBwcmVzZXJ2YWNpw7NuIHkgYWNjZXNvLgoKVXN0ZWQgZGVjbGFyYSBxdWUgZWwgZG9jdW1lbnRvIGVzIHVuIHRyYWJham8gb3JpZ2luYWwsIHkgcXVlIHRpZW5lIGVsIGRlcmVjaG8gZGUgb3RvcmdhciBsb3MgZGVyZWNob3MgY29udGVuaWRvcyBlbiBlc3RhIGxpY2VuY2lhLiBUYW1iacOpbiBkZWNsYXJhIHF1ZSBzdSBwZXRpY2nDs24gbm8gaW5mcmluZ2UgbG9zIGRlcmVjaG9zIGRlIGF1dG9yIGRlIG5hZGllLgoKU2kgZWwgZG9jdW1lbnRvIGNvbnRpZW5lIG1hdGVyaWFsZXMgcGFyYSBsb3MgcXVlIG5vIHNlIHRpZW5lbiBsb3MgZGVyZWNob3MgZGUgYXV0b3IsIHVzdGVkIGRlY2xhcmEgcXVlIGhhIG9idGVuaWRvIGVsIHBlcm1pc28gc2luIHJlc3RyaWNjacOzbiBkZWwgcHJvcGlldGFyaW8gZGUgbG9zIGRlcmVjaG9zIHkgcXVlIGVuIGRpY2hvIG1hdGVyaWFsLCBlc3TDoSBjbGFyYW1lbnRlIGlkZW50aWZpY2FkYSB5IHJlY29ub2NpZGEgc3UgYXV0b3LDrWEgZGVudHJvIGVsIHRleHRvIG8gZGVsIGNvbnRlbmlkbyBkZSBkaWNobyBkb2N1bWVudG8uCgpTaSBlbCBlbnbDrW8gc2UgYmFzYSBlbiB1biB0cmFiYWpvIHF1ZSBoYSBzaWRvIHBhdHJvY2luYWRvIG8gYXBveWFkbyBwb3IgdW5hIGFnZW5jaWEgdSBvcmdhbml6YWNpw7NuIGRpc3RpbnRhIGEgUkVQSVNBTFVELCB1c3RlZCBhY2VwdGEgcXVlIGhhIGN1bXBsaWRvIGNvbiBlbCBkZXJlY2hvIGRlIHJldmlzacOzbiB5IG90cmFzIG9ibGlnYWNpb25lcyByZXF1ZXJpZGFzIHBvciBjb250cmF0byBvIGFjdWVyZG8uCgpSRVBJU0FMVUQgaWRlbnRpZmljYXLDoSBjbGFyYW1lbnRlIHN1KHMpIG5vbWJyZShzKSBjb21vIGF1dG9yKHMpIG8gcHJvcGlldGFyaW8ocykgZGVsIGRvY3VtZW50bywgeSBubyBoYXLDoSBuaW5ndW5hIGFsdGVyYWNpw7NuLCBleGNlcHRvIHNlZ8O6biBsbyBwZXJtaXRpZG8gcG9yIGVzdGEgbGljZW5jaWEuCg== URL https://repisalud.isciii.es/bitstreams/2a4a4cfe-4dea-4fa7-9c95-76bf68a197fb/download File MD5 f5b02623a3985d3cd2ff9492946dc142 4648588 application/pdf Aclinicallycompatibledrug-screening_2022.pdf URL https://repisalud.isciii.es/bitstreams/4dd622bb-6062-4b79-98b0-aec4d5e590d7/download File MD5 e3cfd29866b62a8a1fd89e0dc0e7def9 100453 text/plain Aclinicallycompatibledrug-screening_2022.pdf.txt