Patient-derived resources for decoding and targeting brain metastases ecosystems
EMBO Molecular Medicine, vol. 18, pp. 3017–3027
Abstract
Brain metastases (BrM) affect up to 30% of patients with solid tumors, yet durable intracranial control remains rare, and the biological drivers of this poor prognosis are incompletely understood. Patient-derived resources, such as clinical cohorts, biobanks, functional ex vivo models, and multi-omic platforms, are central to closing this gap, but their generation and integration face substantial logistical and technical hurdles. Drawing on the RISEbrain consortium's experience, this Perspective examines BrM-focused cohorts and biobanks, highlighting the underused potential of rapid autopsy programs to capture early metastatic seeding. We discuss patient-derived organotypic cultures and emerging organoid-based "avatar" systems as functional platforms for therapeutic profiling, alongside the complementary strengths of bulk and single-cell/-nucleus transcriptomics. We outline how spatial transcriptomics and proteomics are resolving the architecture of the BrM microenvironment, and assess liquid biopsy approaches, including emerging photonic biosensors, for non-invasive monitoring. Together, these resources form an interdependent toolkit whose coordinated deployment will advance early detection, prevention, and precision treatment of BrM.
Authors 25
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Spanish National Cancer Research Centre
Affiliation as printed
Brain Metastasis Group, Spanish National Cancer Research Centre, Madrid, Spain. mvaliente@cnio.es
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Lal Era Aydoğan Aachen Department of Hematology, Oncology Medical Faculty Center for Integrated Oncology
Affiliation as printed
Department of Hematology, Oncology, Hemostaseology, Stem Cell Transplantation, Medical Faculty, Center for Integrated Oncology (CIO) RWTH Aachen University, Aachen, Germany
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Affiliation as printed
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
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Technische Universität Dresden
Affiliation as printed
Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany
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Spanish National Cancer Research Centre
Affiliation as printed
Brain Metastasis Group, Spanish National Cancer Research Centre, Madrid, Spain
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Technische Universität Dresden
Affiliation as printed
Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany
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Affiliation as printed
Biomedical Science and Engineering, Koç University, Istanbul, Türkiye
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Spanish National Cancer Research Centre
Affiliation as printed
CNIO Biobank, Spanish National Cancer Research Centre, Madrid, Spain
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Spanish National Cancer Research Centre
Affiliation as printed
Brain Metastasis Group, Spanish National Cancer Research Centre, Madrid, Spain
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Affiliation as printed
Pathology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
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Affiliation as printed
Pathology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
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Affiliation as printed
Pathology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
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Spanish National Cancer Research Centre
Affiliation as printed
Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
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Technische Universität Dresden
Affiliation as printed
Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany
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Spanish National Cancer Research Centre
Affiliation as printed
Brain Metastasis Group, Spanish National Cancer Research Centre, Madrid, Spain
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Goethe University Frankfurt · Frankfurt Cancer Institute
Affiliation as printed
Frankfurt Cancer Institute (FCI), Goethe University Frankfurt, Frankfurt am Main, Germany
Goethe University Frankfurt, Neurological Institute (Edinger Institute), Frankfurt am Main, Germany
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German Cancer Research Center · Helmholtz-Zentrum Dresden-Rossendorf · University Hospital Carl Gustav Carus · Nationales Centrum für Tumorerkrankungen Dresden · German Cancer Consortium (DKTK) Dresden · Technische Universität Dresden
Affiliation as printed
German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany
Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany
National Center for Tumor Diseases (NCT/UCC) Dresden, a partnership between DKFZ, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, and Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
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Goethe University Frankfurt · University Hospital Frankfurt · Frankfurt Cancer Institute
Affiliation as printed
Department of Neurosurgery, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany
Frankfurt Cancer Institute (FCI), Goethe University Frankfurt, Frankfurt am Main, Germany
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Goethe University Frankfurt · University Hospital Frankfurt · Frankfurt Cancer Institute
Affiliation as printed
Department of Neurosurgery, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany
Frankfurt Cancer Institute (FCI), Goethe University Frankfurt, Frankfurt am Main, Germany
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Affiliation as printed
Biomedical Science and Engineering, Koç University, Istanbul, Türkiye
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Spanish National Cancer Research Centre
Affiliation as printed
Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
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Affiliation as printed
Pathology Unit, Department of Medical Sciences, University of Turin, Turin, Italy
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German Cancer Research Center · Helmholtz-Zentrum Dresden-Rossendorf · University Hospital Carl Gustav Carus · Nationales Centrum für Tumorerkrankungen Dresden · German Cancer Consortium (DKTK) Dresden · Technische Universität Dresden
Affiliation as printed
German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany
Institute of Immunology, Faculty of Medicine Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany
National Center for Tumor Diseases (NCT/UCC) Dresden, a partnership between DKFZ, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, and Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany
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Affiliation as printed
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
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Hind Medyouf Aachen Department of Hematology, Oncology Medical Faculty Center for Integrated Oncology
Affiliation as printed
Department of Hematology, Oncology, Hemostaseology, Stem Cell Transplantation, Medical Faculty, Center for Integrated Oncology (CIO) RWTH Aachen University, Aachen, Germany. hmedyouf@ukaachen.de
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