PXD020092-1

PXD020092 is an original dataset announced via ProteomeXchange.

Title	Identification of brain metastasis vulnerabilities using METPlatform
Description	Exclusion of cancer patients with brain metastases from clinical trials is a major cause of the limited therapeutic options available for secondary brain tumors. Here, we report a novel drug-screening platform (METPlatform) based on organotypic cultures that allows identifying anti-metastatic compounds in a preparation that includes the tumor microenvironment. By applying this approach to brain metastasis, we identified HSP90 as a promising therapeutic target. A blood-brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases from melanoma, lung and breast adenocarcinoma with distinct oncogenomic profiles at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis of brain metastases treated with the chaperone inhibitor revealed non-canonical clients of HSP90 as potential novel mediators of brain metastasis and actionable mechanisms of resistance driven by autophagy. Our work validates METPlatform as a potent resource for metastasis research integrating drug-screening and unbiased omic approaches that is fully compatible with human samples. We envision that METPlatform could be established as a clinically relevant strategy to personalize the management of metastatic disease in the brain and elsewhere.
HostingRepository	PRIDE
AnnounceDate	2022-03-17
AnnouncementXML	Submission_2022-03-17_00:05:55.822.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Javier Munoz
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-29 03:22:06	ID requested
⏵ 1	2022-03-17 00:05:56	announced
2	2024-10-22 05:35:30	announced	2024-10-22: Updated project metadata.

Zhu L, Retana D, Garc, í, a-G, ó, mez P, Á, lvaro-Espinosa L, Priego N, Masmudi-Mart, í, n M, Yebra N, Miarka L, Hern, á, ndez-Encinas E, Blanco-Aparicio C, Mart, í, nez S, Sobrino C, Ajenjo N, Artiga MJ, Ortega-Paino E, Torres-Ruiz R, Rodr, í, guez-Perales S, Soffietti R, Bertero L, Cassoni P, Weiss T, Mu, ñ, oz J, Sep, ú, lveda JM, Gonz, á, lez-Le, ó, n P, Jim, é, nez-Rold, á, n L, Moreno LM, Esteban O, P, é, rez-N, ú, ñ, ez Á, Hern, á, ndez-La, í, n A, Toldos O, Ruano Y, Alc, á, zar L, Blasco G, Fern, á, ndez-Al, é, n J, Caleiras E, Lafarga M, Meg, í, as D, Gra, ñ, a-Castro O, N, ö, r C, Taylor MD, Young LS, Vare, š, lija D, Cosgrove N, Couch FJ, Cuss, ó L, Desco M, Mouron S, Quintela-Fandino M, Weller M, Pastor J, Valiente M, de la Lama-Zaragoza A, Calero-Felix L, Fia, ñ, o-Valverde C, Delgado-L, ó, pez PD, Montalvo-Afonso A, Pascual-Llorente M, D, í, az-Piqueras Á, Nam-Cha SH, Barrena L, ó, pez C, Plans Ahicart G, Mart, í, nez-Saez E, Ram, ó, n Y Cajal S, Nicol, á, s P, A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis. EMBO Mol Med, 14(3):e14552(2022) [pubmed]

submitter keyword: brain metastasis, metplatform, in situ proteomics

Javier Muñoz
contact affiliation	Spanish National Cancer Research Center (CNIO)
contact email	jmunozpe@cnio.es
lab head
Javier Munoz
contact affiliation	CNIO
contact email	jmunozpe@cnio.es
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/03/PXD020092

PRIDE project URI

• PRIDE
  1. PXD020092
     1. Label: PRIDE project
     2. Name: Identification of brain metastasis vulnerabilities using METPlatform