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

Simple item page
dc.contributor.authorZhu, Lucía
dc.contributor.authorRetana, Diana
dc.contributor.authorGarcía-Gómez, Pedro
dc.contributor.authorÁlvaro-Espinosa, Laura
dc.contributor.authorPriego, Neibla
dc.contributor.authorMasmudi-Martín, Mariam
dc.contributor.authorYebra, Natalia
dc.contributor.authorMiarka, Lauritz
dc.contributor.authorHernández-Encinas, Elena
dc.contributor.authorBlanco-Aparicio, Carmen
dc.contributor.authorMartínez, Sonia
dc.contributor.authorSobrino, Cecilia
dc.contributor.authorAjenjo, Nuria
dc.contributor.authorArtiga, Maria-Jesus
dc.contributor.authorOrtega-Paino, Eva
dc.contributor.authorTorres-Ruiz, Raúl
dc.contributor.authorRodríguez-Perales, Sandra
dc.contributor.authorSoffietti, Riccardo
dc.contributor.authorBertero, Luca
dc.contributor.authorCassoni, Paola
dc.contributor.authorWeiss, Tobias
dc.contributor.authorMuñoz, Javier
dc.contributor.authorSepúlveda, Juan Manuel
dc.contributor.authorGonzález-León, Pedro
dc.contributor.authorJiménez-Roldán, Luis
dc.contributor.authorMoreno, Luis Miguel
dc.contributor.authorEsteban, Olga
dc.contributor.authorPérez-Núñez, Ángel
dc.contributor.authorHernández-Laín, Aurelio
dc.contributor.authorToldos, Oscar
dc.contributor.authorRuano, Yolanda
dc.contributor.authorAlcázar, Lucía
dc.contributor.authorBlasco, Guillermo
dc.contributor.authorFernández-Alén, José
dc.contributor.authorCaleiras, Eduardo
dc.contributor.authorLafarga, Miguel
dc.contributor.authorMegias Vazquez, Diego
dc.contributor.authorGraña-Castro, Osvaldo
dc.contributor.authorNör, Carolina
dc.contributor.authorTaylor, Michael D
dc.contributor.authorYoung, Leonie S
dc.contributor.authorVarešlija, Damir
dc.contributor.authorCosgrove, Nicola
dc.contributor.authorCouch, Fergus J
dc.contributor.authorCussó, Lorena
dc.contributor.authorDesco, Manuel
dc.contributor.authorMouron, Silvana
dc.contributor.authorQuintela-Fandino, Miguel
dc.contributor.authorWeller, Michael
dc.contributor.authorPastor, Joaquín
dc.contributor.authorValiente, Manuel
dc.contributor.funderMinisterio de Economía, Innovación y Competitividad (España)
dc.contributor.funderFundación Fero
dc.contributor.funderFundación La Marató TV3
dc.contributor.funderMelanoma Research Alliance
dc.contributor.funderFundación Ramón Areces
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
dc.contributor.funderScience Foundation Ireland
dc.contributor.funderFundación La Caixa
dc.contributor.funderBoehringer Ingelheim Fonds
dc.contributor.funderMinisterio de Ciencia e Innovación (España)
dc.contributor.funderMinisterio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
dc.contributor.funderFundación ProCNIC
dc.date.accessioned2023-03-22T13:15:26Z
dc.date.available2023-03-22T13:15:26Z
dc.date.issued2022-03-07
dc.description.abstractWe 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.es_ES
dc.description.peerreviewedSíes_ES
dc.description.sponsorshipWe want to thank all members from the Brain Metastasis Group, F.X. Real, M. Malumbres, and M. Barbacid for critical discussion of the manuscript, the CNIO Core Facilities for their excellent assistance, Antonio Cebri a and Javier Klett for their excellent assistance in drug-screening, Sonsoles RodrıguezArıstegui for her excellent work with preparation of different compounds and Alexandra de Francisco, Yolanda Sierra, and Marıa de la Jara Felipe for their excellent work with animal preparation and imaging protocols. We also thank J. Massague (MSKCC) for some of the BrM cell lines. This work was supported by MINECO (SAF2017-89643-R, SAF2014-57243-R, SAF2015-62547-ERC) (M.V.), Fundacion FERO (IX FERO Grant for Research in Oncology) (M.V.), Fundacio La Marato de TV 3 (141) (M.V.), Melanoma Research Alliance (Bristol-Myers Squibb-Melanoma Research Alliance Young Investigator Award 2017 (https:// doi.org/10.48050/pc.gr.75716)) (M.V.), Beug Foundation (Prize for Metastasis Research 2017) (M.V.), Fundacion Ramon Areces (CIVP19S8163) (M.V.) and CIVP20S10662 (E.O.P.), Worldwide Cancer Research (19-0177) (M.V.), H2020- FETOPEN (828972) (M.V.), Cancer Research Institute (Clinic and Laboratory Integration Program CRI Award 2018 (54545)) (M.V.), AECC (Coordinated Translational Groups 2017 (GCTRA16015SEOA) (M.V.), LAB AECC 2019 (LABAE19002- VALI) (M.V.), ERC CoG (864759) (M.V.), Sophien-Stiftung zur Förderung der klinischen Krebsforschung (T.W.), Promedica Stiftung (T.W.), Stiftung fur ange- € wandte Krebsforschung (T.W.), Forschungskredit of the University of Zurich (FK-18-054) (T.W.), Betty and David Koetser Foundation for Brain Research (T.W.), Foundation for Applied Cancer Research in Zurich (T.W., M.W.), Comunidad de Madrid (S2017/BMD-3867 RENIM-CM and Y2018/NMT-4949 NanoLiver-CM) and European structural and investment funds (M.D.), ISCIII (PT20/00044) co-funded by FEDER “A way of making Europe” (M.D.), Ministero dell’Istruzione, dell’Universit a e della Ricerca-MIUR, “Dipartimenti di Eccellenza 2018-2022”, (D15D18000410001) (L.B. and P.C.), Science Foundation Ireland Frontiers for the Future Award (19/FFP/6443) (L.Y.), Science Foundation Ireland Strategic Partnership Programme, Precision Oncology Ireland (18/SPP/3522) (L.Y.), Breast Cancer Now Fellowship Award/ with the generous support of Walk the Walk (2019AugSF1310) (D.V.), La Caixa-Severo Ochoa International PhD Program Fellowship (LCF/BQ/SO16/52270014) (L.Z.), La Caixa International PhD Program Fellowship-Marie Sklodowska-Curie (LCF/BQ/DI17/11620028) (P.G-G), MINECO-Severo Ochoa PhD Fellowship (BES-2017-081995) (L.A-E.), AECC Postdoctoral Fellowship (POSTD19016PRIE) (N.P.), Boehringer Ingelheim Fonds MD fellowship (L.M.). The contribution of the Experimental Therapeutics Programme was supported by core funding from the Spanish National Cancer Research Center (CNIO). CNIO is supported by the ISCIII, the Ministerio de Ciencia e Innovacion, and is a Severo Ochoa Center of Excellence (SEV- 2015-0510). The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovacion and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). M.V. was named Ramon y Cajal Investigator (RYC2013-13365) and is member of EMBO YIP (4053).es_ES
dc.format.number3es_ES
dc.format.pagee14552es_ES
dc.format.volume14es_ES
dc.identifier.citationEMBO Mol Med. 2022 Mar 7;14(3):e14552es_ES
dc.identifier.doi10.15252/emmm.202114552es_ES
dc.identifier.e-issn1757-4684es_ES
dc.identifier.journalEMBO molecular medicinees_ES
dc.identifier.pubmedID35174975es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/15688
dc.language.isoenges_ES
dc.publisherEMBO Press
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/SAF2017-89643-Res_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/SAF2014-57243-Res_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/SAF2015-62547-ERCes_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/CIVP19S8163es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/CIVP20S10662es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/S2017/BMD-3867 RENIM-CMes_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/Y2018/NMT-4949es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/PT20/00044es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/LCF/BQ/SO16/52270014es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/BES-2017-081995es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/POSTD19016PRIEes_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/RYC2013-13365es_ES
dc.relation.projectFECYTinfo:eu-repo/grantAgreement/ES/SEV-2015-0510es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/H2020-FETOPEN/828972es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/LCF/BQ/DI17/11620028es_ES
dc.relation.publisherversion10.15252/emmm.202114552es_ES
dc.repisalud.institucionCNICes_ES
dc.repisalud.orgCNICCNIC::Unidades técnicas::Imagen Avanzadaes_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subject.meshAntineoplastic Agentses_ES
dc.subject.meshBrain Neoplasmses_ES
dc.subject.meshAnimalses_ES
dc.subject.meshBlood-Brain Barrieres_ES
dc.subject.meshMicees_ES
dc.subject.meshNeoplasm Recurrence, Locales_ES
dc.subject.meshProteomicses_ES
dc.titleA clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis.es_ES
dc.typejournal articlees_ES
dc.type.hasVersionVoRes_ES
dspace.entity.typePublication
relation.isAuthorOfPublicationa3f252c1-42db-424e-b605-b184f09426bb
relation.isAuthorOfPublication331a622c-8ee3-4e36-beeb-e39af23bf4e5
relation.isAuthorOfPublication5bff0e9a-1479-4c96-a679-ddd701a7107a
relation.isAuthorOfPublication5b516c49-9db7-445a-b1ad-795bb898b37a
relation.isAuthorOfPublication3d8c68c5-1cf7-41e7-bc20-a44a703ae994
relation.isAuthorOfPublication9ff41ae3-2484-4d1c-bfb4-9f7a64487317
relation.isAuthorOfPublication.latestForDiscoverya3f252c1-42db-424e-b605-b184f09426bb
relation.isFunderOfPublication7f58fe23-580a-4b32-b53f-6fbe98250bdc
relation.isFunderOfPublication024bfa3c-a064-4759-9aac-0d6566f28764
relation.isFunderOfPublicationff637ff5-6bbe-4cb4-917f-84200711c119
relation.isFunderOfPublication9b854a61-30e3-4322-8b1e-8aad1d5c5d6c
relation.isFunderOfPublication3d244836-0b9b-4476-8411-efb30ba10d7f
relation.isFunderOfPublicationefa64f05-b985-4984-8f1e-5fc4ef21f502
relation.isFunderOfPublication90c15883-5c89-4576-9d05-5eebfc41784b
relation.isFunderOfPublicationf04d23ec-a91d-4242-88b0-cc436888f8a2
relation.isFunderOfPublication6e3d618b-53a8-47e9-ab5f-637382022607
relation.isFunderOfPublication289dce42-6a28-4892-b0a8-c70c46cbb185
relation.isFunderOfPublication9bec53f6-b1d2-4340-9f6b-91815956d602
relation.isFunderOfPublicationef935eeb-4c46-446a-868e-66e905683e75
relation.isFunderOfPublication.latestForDiscovery7f58fe23-580a-4b32-b53f-6fbe98250bdc
relation.isPublisherOfPublication4edc911e-c13d-4057-ad87-3d71fc21d024
relation.isPublisherOfPublication.latestForDiscovery4edc911e-c13d-4057-ad87-3d71fc21d024

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
A clinically compatible drug-screening EMBO Mol Med 2022.pdf
Size:
4.4 MB
Format:
Adobe Portable Document Format
Description:
Artículo
Download

Collections

Grupos de investigación
Grupos de investigación