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

RENACER

doi:10.15252/emmm.202114552

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

RENACER

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Article number	e14552
Journal	EMBO Molecular Medicine
Volume	14
Issue number	3
DOIs	https://doi.org/10.15252/emmm.202114552
State	Published - Mar 7 2022

Keywords

drug-screen
metastasis
organotypic cultures
patient-derived
resistance

ASJC Scopus subject areas

Molecular Medicine

Access to Document

10.15252/emmm.202114552

Cite this

@article{6c2107f9cbf647ffa787d22e4f8e84aa,

title = "A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis",

abstract = "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.",

keywords = "drug-screen, metastasis, organotypic cultures, patient-derived, resistance",

author = "RENACER and Luc{\'i}a Zhu and Diana Retana and Pedro Garc{\'i}a-G{\'o}mez and Laura {\'A}lvaro-Espinosa and Neibla Priego and Mariam Masmudi-Mart{\'i}n and Natalia Yebra and Lauritz Miarka and Elena Hern{\'a}ndez-Encinas and Carmen Blanco-Aparicio and Sonia Mart{\'i}nez and Cecilia Sobrino and Nuria Ajenjo and Artiga, {Maria Jesus} and Eva Ortega-Paino and Ra{\'u}l Torres-Ruiz and Sandra Rodr{\'i}guez-Perales and Riccardo Soffietti and Luca Bertero and Paola Cassoni and Tobias Weiss and Javier Mu{\~n}oz and Sep{\'u}lveda, {Juan Manuel} and Pedro Gonz{\'a}lez-Le{\'o}n and Luis Jim{\'e}nez-Rold{\'a}n and Moreno, {Luis Miguel} and Olga Esteban and {\'A}ngel P{\'e}rez-N{\'u}{\~n}ez and Aurelio Hern{\'a}ndez-La{\'i}n and Oscar Toldos and Yolanda Ruano and Luc{\'i}a Alc{\'a}zar and Guillermo Blasco and Jos{\'e} Fern{\'a}ndez-Al{\'e}n and Eduardo Caleiras and Miguel Lafarga and Diego Meg{\'i}as and Osvaldo Gra{\~n}a-Castro and Carolina N{\"o}r and Taylor, {Michael D.} and Young, {Leonie S.} and Damir Vare{\v s}lija and Nicola Cosgrove and Couch, {Fergus J.} and Lorena Cuss{\'o} and Manuel Desco and Silvana Mouron and Miguel Quintela-Fandino and Michael Weller and Joaqu{\'i}n Pastor",

note = "Funding Information: We 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 Rodr{\'i}guez-Ar{\'i}stegui for her excellent work with preparation of different compounds and Alexandra de Francisco, Yolanda Sierra, and Mar{\'i}a de la Jara Felipe for their excellent work with animal preparation and imaging protocols. We also thank J. Massagu{\'e} (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.), Fundaci{\'o}n FERO (IX FERO Grant for Research in Oncology) (M.V.), Fundaci{\'o} La Marat{\'o} de TV3 (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.), Fundaci{\'o}n Ram{\'o}n 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 (LABAE19002VALI) (M.V.), ERC CoG (864759) (M.V.), Sophien-Stiftung zur F{\"o}rderung der klinischen Krebsforschung (T.W.), Promedica Stiftung (T.W.), Stiftung f{\"u}r angewandte 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 Innovaci{\'o}n, and is a Severo Ochoa Center of Excellence (SEV-2015-0510). The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovaci{\'o}n and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). M.V. was named Ram{\'o}n y Cajal Investigator (RYC-2013-13365) and is member of EMBO YIP (4053). The authors declare that they have no conflict of interest. Funding Information: We 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 Rodr{\'i}guez‐Ar{\'i}stegui for her excellent work with preparation of different compounds and Alexandra de Francisco, Yolanda Sierra, and Mar{\'i}a de la Jara Felipe for their excellent work with animal preparation and imaging protocols. We also thank J. Massagu{\'e} (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.), Fundaci{\'o}n FERO (IX FERO Grant for Research in Oncology) (M.V.), Fundaci{\'o} La Marat{\'o} de TV3 (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.), Fundaci{\'o}n Ram{\'o}n 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 (LABAE19002VALI) (M.V.), ERC CoG (864759) (M.V.), Sophien‐Stiftung zur F{\"o}rderung der klinischen Krebsforschung (T.W.), Promedica Stiftung (T.W.), Stiftung f{\"u}r angewandte 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 Innovaci{\'o}n, and is a Severo Ochoa Center of Excellence (SEV‐2015‐0510). The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovaci{\'o}n and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV‐2015‐0505). M.V. was named Ram{\'o}n y Cajal Investigator (RYC‐2013‐13365) and is member of EMBO YIP (4053). Publisher Copyright: {\textcopyright} 2022 The Authors. Published under the terms of the CC BY 4.0 license.",

year = "2022",

month = mar,

day = "7",

doi = "10.15252/emmm.202114552",

language = "English (US)",

volume = "14",

journal = "EMBO Molecular Medicine",

issn = "1757-4676",

publisher = "Wiley-Blackwell",

number = "3",

}

TY - JOUR

T1 - A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis

AU - RENACER

AU - Zhu, Lucía

AU - Retana, Diana

AU - García-Gómez, Pedro

AU - Álvaro-Espinosa, Laura

AU - Priego, Neibla

AU - Masmudi-Martín, Mariam

AU - Yebra, Natalia

AU - Miarka, Lauritz

AU - Hernández-Encinas, Elena

AU - Blanco-Aparicio, Carmen

AU - Martínez, Sonia

AU - Sobrino, Cecilia

AU - Ajenjo, Nuria

AU - Artiga, Maria Jesus

AU - Ortega-Paino, Eva

AU - Torres-Ruiz, Raúl

AU - Rodríguez-Perales, Sandra

AU - Soffietti, Riccardo

AU - Bertero, Luca

AU - Cassoni, Paola

AU - Weiss, Tobias

AU - Muñoz, Javier

AU - Sepúlveda, Juan Manuel

AU - González-León, Pedro

AU - Jiménez-Roldán, Luis

AU - Moreno, Luis Miguel

AU - Esteban, Olga

AU - Pérez-Núñez, Ángel

AU - Hernández-Laín, Aurelio

AU - Toldos, Oscar

AU - Ruano, Yolanda

AU - Alcázar, Lucía

AU - Blasco, Guillermo

AU - Fernández-Alén, José

AU - Caleiras, Eduardo

AU - Lafarga, Miguel

AU - Megías, Diego

AU - Graña-Castro, Osvaldo

AU - Nör, Carolina

AU - Taylor, Michael D.

AU - Young, Leonie S.

AU - Varešlija, Damir

AU - Cosgrove, Nicola

AU - Couch, Fergus J.

AU - Cussó, Lorena

AU - Desco, Manuel

AU - Mouron, Silvana

AU - Quintela-Fandino, Miguel

AU - Weller, Michael

AU - Pastor, Joaquín

N1 - Funding Information: We 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 Cebriá and Javier Klett for their excellent assistance in drug-screening, Sonsoles Rodríguez-Arístegui for her excellent work with preparation of different compounds and Alexandra de Francisco, Yolanda Sierra, and María de la Jara Felipe for their excellent work with animal preparation and imaging protocols. We also thank J. Massagué (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.), Fundación FERO (IX FERO Grant for Research in Oncology) (M.V.), Fundació La Marató de TV3 (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.), Fundación Ramón 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 (LABAE19002VALI) (M.V.), ERC CoG (864759) (M.V.), Sophien-Stiftung zur Förderung der klinischen Krebsforschung (T.W.), Promedica Stiftung (T.W.), Stiftung für angewandte 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'Università 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 Innovación, and is a Severo Ochoa Center of Excellence (SEV-2015-0510). The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovación and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). M.V. was named Ramón y Cajal Investigator (RYC-2013-13365) and is member of EMBO YIP (4053). The authors declare that they have no conflict of interest. Funding Information: We 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 Cebriá and Javier Klett for their excellent assistance in drug‐screening, Sonsoles Rodríguez‐Arístegui for her excellent work with preparation of different compounds and Alexandra de Francisco, Yolanda Sierra, and María de la Jara Felipe for their excellent work with animal preparation and imaging protocols. We also thank J. Massagué (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.), Fundación FERO (IX FERO Grant for Research in Oncology) (M.V.), Fundació La Marató de TV3 (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.), Fundación Ramón 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 (LABAE19002VALI) (M.V.), ERC CoG (864759) (M.V.), Sophien‐Stiftung zur Förderung der klinischen Krebsforschung (T.W.), Promedica Stiftung (T.W.), Stiftung für angewandte 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'Università 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 Innovación, and is a Severo Ochoa Center of Excellence (SEV‐2015‐0510). The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovación and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV‐2015‐0505). M.V. was named Ramón y Cajal Investigator (RYC‐2013‐13365) and is member of EMBO YIP (4053). Publisher Copyright: © 2022 The Authors. Published under the terms of the CC BY 4.0 license.

PY - 2022/3/7

Y1 - 2022/3/7

N2 - 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.

AB - 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.

KW - drug-screen

KW - metastasis

KW - organotypic cultures

KW - patient-derived

KW - resistance

UR - http://www.scopus.com/inward/record.url?scp=85125882089&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85125882089&partnerID=8YFLogxK

U2 - 10.15252/emmm.202114552

DO - 10.15252/emmm.202114552

M3 - Article

C2 - 35174975

AN - SCOPUS:85125882089

SN - 1757-4676

VL - 14

JO - EMBO Molecular Medicine

JF - EMBO Molecular Medicine

IS - 3

M1 - e14552

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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