drug_screening

Drug screening

Zhu et al. reported a medium-throughput drug-screening platform (METPlatform) based on organotypic cultures that allow evaluating inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastases, they 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. The work validates METPlatform as a potent resource for metastasis research integrating drug screening and unbiased omic approaches that are compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere 1).


1)
Zhu L, Retana D, García-Gómez P, Álvaro-Espinosa L, Priego N, Masmudi-Martín M, Yebra N, Miarka L, Hernández-Encinas E, Blanco-Aparicio C, Martínez S, Sobrino C, Ajenjo N, Artiga MJ, Ortega-Paino E, Torres-Ruiz R, Rodríguez-Perales S; RENACER, Soffietti R, Bertero L, Cassoni P, Weiss T, Muñoz J, Sepúlveda JM, González-León P, Jiménez-Roldán L, Moreno LM, Esteban O, Pérez-Núñez Á, Hernández-Laín A, Toldos O, Ruano Y, Alcázar L, Blasco G, Fernández-Alén J, Caleiras E, Lafarga M, Megías D, Graña-Castro O, Nör C, Taylor MD, Young LS, Varešlija D, Cosgrove N, Couch FJ, Cussó L, Desco M, Mouron S, Quintela-Fandino M, Weller M, Pastor J, Valiente M. A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis. EMBO Mol Med. 2022 Feb 17:e14552. doi: 10.15252/emmm.202114552. Epub ahead of print. PMID: 35174975.
  • drug_screening.txt
  • Last modified: 2022/02/17 20:09
  • by administrador