Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/15688
Título
A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis.
Autor(es)
Zhu, Lucía | Retana, Diana CNIO | García-Gómez, Pedro | Álvaro-Espinosa, Laura | Priego, Neibla | Masmudi-Martín, Mariam | Yebra, Natalia | Miarka, Lauritz | Hernández-Encinas, Elena | Blanco-Aparicio, Carmen CNIO | Martínez, Sonia | Sobrino, Cecilia | Ajenjo, Nuria CNIO | Artiga, Maria-Jesus | Ortega-Paino, Eva | Torres-Ruiz, Raúl | Rodríguez-Perales, Sandra | Soffietti, Riccardo | Bertero, Luca | Cassoni, Paola | Weiss, Tobias | Muñoz, Javier | Sepúlveda, Juan Manuel | González-León, Pedro | Jiménez-Roldán, Luis | Moreno, Luis Miguel | Esteban, Olga | Pérez-Núñez, Ángel | Hernández-Laín, Aurelio | Toldos, Oscar | Ruano, Yolanda | Alcázar, Lucía | Blasco, Guillermo | Fernández-Alén, José | Caleiras, Eduardo | Lafarga, Miguel | Megias Vazquez, Diego CNIO | Graña-Castro, Osvaldo CNIO | Nör, Carolina | Taylor, Michael D | Young, Leonie S | Varešlija, Damir | Cosgrove, Nicola | Couch, Fergus J | Cussó, Lorena | Desco, Manuel CNIC | Mouron, Silvana | Quintela-Fandino, Miguel | Weller, Michael | Pastor, Joaquín | Valiente, Manuel CNIO
Fecha de publicación
2022-03-07
Cita
EMBO Mol Med. 2022 Mar 7;14(3):e14552
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
MESH
Antineoplastic Agents | Brain Neoplasms | Animals | Blood-Brain Barrier | Mice | Neoplasm Recurrence, Local | Proteomics
Versión en línea
DOI
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