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A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis.

Identificadores del recurso

1757-4684

https://hdl.handle.net/10641/3264

10.15252/emmm.202114552

Procedencia

(Repositorio Institucional de la Universidad Francisco de Vitoria)

Ficha

Título:: A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis.
Descripción:: 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.; post-print; 4540 KB
Idioma:: English
Relación:: https://www.embopress.org/doi/full/10.15252/emmm.202114552
Autor/Productor:: Zhu, Lucıa; Ruano Domínguez, Yolanda; Valiente, Manuel
Editor:: EMBO Molecular Medicine
Derechos:: Atribución-NoComercial-SinDerivadas 3.0 España; http://creativecommons.org/licenses/by-nc-nd/3.0/es/; openAccess
Fecha:: 2023-02-16T12:08:34Z; 2022
Tipo de recurso:: article

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