ArticleNature medicine2022
Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism.
Open access · hybridAbstract read
In one paragraph
Article in Nature medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 1 pooled it
6.3field-weighted citation impact, top 2% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Focal Adhesion Kinase (FAK)-Hippo/YAP transduction signaling mediates the stimulatory effects exerted by S100A8/A9-RAGE system in triple-negative breast cancer (TNBC).Journal of experimental & clinical cancer research : CR · 2022Pooled it
- Machine learning-based prognostic model and single-cell transcriptomic integration for identifying brain metastasis-associated malignant subpopulations and potential therapeutic targets in lung adenocarcinoma.Cancer cell international · 2026Article
- Astrocyte-driven immunosuppression in the brain tumor microenvironment.Nature immunology · 2026Review
- The impact of CHEK2 status on radiosurgical outcomes in breast cancer brain metastases.Neurosurgical review · 2026Article
- Fecal Detection of Calprotectin Subunits Links Inflammatory Bowel Disease Activity With Chronicity of Intestinal Inflammation.Gastroenterology · 2026Article
- The evolving landscape of brain metastasis: volume II.Trends in cancer · 2026Review
- Serum S100A8/S100A9 is associated with increased risk of brain metastasis in patients with inflammatory breast cancer.medRxiv : the preprint server for health sciences · 2026Article
- The neuro-immune-vascular landscape of lung cancer brain metastasis: insights from organoid models.Frontiers in immunology · 2026Review
- USP33 Promotes Lung Adenocarcinoma Brain Metastasis by Inhibiting the K48-Linked Ubiquitination and Degradation of S100A9 and Facilitating Vimentin Secretion.International journal of biological sciences · 2026Article
- S100A9 enhances tumor immune suppression and cancer cell survival in small cell lung cancer.Cell death & disease · 2025Article
- Hyperglycemia is associated with poor survival in patients with brain metastases treated with radiotherapy.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2025Article
- Article
- Modeling metastasis - leveraging novel tools to streamline discovery in advanced cancer.Disease models & mechanisms · 2025Review
- Advanced Glycation End Products in Disease Development and Potential Interventions.Antioxidants (Basel, Switzerland) · 2025Review
- Targeting S100A8/A9-NCF1 axis in tumor microenvironment to prevent tumor metastasis by self-assembled peptide nanofibers.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Multidisciplinary management strategies for recurrent brain metastasis after prior radiotherapy: An overview.Neuro-oncology · 2025Review
- Mucin 5AC Promotes Breast Cancer Brain Metastasis through cMET/CD44v6.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Molecular evolution of central nervous system metastasis and therapeutic implications.Trends in molecular medicine · 2025Review
- Cancer brain metastasis: molecular mechanisms and therapeutic strategies.Molecular biomedicine · 2025Review
- Potential of ex vivo organotypic slice cultures in neuro-oncology.Neuro-oncology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
67 authors at 20 institutions in 9 countries.
Cátia Monteiro *Brain Metastasis Group, CNIO, Madrid, Spain.
Lauritz Miarka *Brain Metastasis Group, CNIO, Madrid, Spain.
María Perea-GarcíaBrain Metastasis Group, CNIO, Madrid, Spain.
Neibla PriegoBrain Metastasis Group, CNIO, Madrid, Spain.
Pedro García-GómezBrain Metastasis Group, CNIO, Madrid, Spain.ORCID http://orcid.org/0000-0003-0694-3942
Laura Álvaro-EspinosaBrain Metastasis Group, CNIO, Madrid, Spain.
Ana de Pablos-AragonesesBrain Metastasis Group, CNIO, Madrid, Spain.
Natalia YebraBrain Metastasis Group, CNIO, Madrid, Spain.
Diana RetanaBrain Metastasis Group, CNIO, Madrid, Spain.
Patricia BaenaBrain Metastasis Group, CNIO, Madrid, Spain.
Coral Fustero-TorreBioinformatics Unit, CNIO, Madrid, Spain.ORCID http://orcid.org/0000-0001-5504-4164
Osvaldo Graña-CastroBioinformatics Unit, CNIO, Madrid, Spain.
Kevin TrouléBioinformatics Unit, CNIO, Madrid, Spain.
Eduardo CaleirasHistopathology Core Unit, CNIO, Madrid, Spain.
Patricia TezanosDepartment of Translational Neuroscience, Cajal Institute, CSIC, Madrid, Spain.ORCID http://orcid.org/0000-0002-0734-9913
Pablo MuelaDepartment of Translational Neuroscience, Cajal Institute, CSIC, Madrid, Spain.ORCID http://orcid.org/0000-0001-5032-2129
Elisa CintadoDepartment of Translational Neuroscience, Cajal Institute, CSIC, Madrid, Spain.ORCID http://orcid.org/0000-0002-1943-4664
José Luis TrejoDepartment of Translational Neuroscience, Cajal Institute, CSIC, Madrid, Spain.ORCID http://orcid.org/0000-0003-0618-5547
Juan Manuel SepúlvedaNeuro-Oncology Unit, Hospital Universitario 12 de Octubre, Madrid, Spain.
Pedro González-LeónNeurosurgery Unit, Hospital Universitario 12 de Octubre, Madrid, Spain.
Luis Jiménez-RoldánNeurosurgery Unit, Hospital Universitario 12 de Octubre, Madrid, Spain.
Luis Miguel MorenoNeurosurgery Unit, Hospital Universitario 12 de Octubre, Madrid, Spain.
Olga EstebanNeurosurgery Unit, Hospital Universitario 12 de Octubre, Madrid, Spain.
Ángel Pérez-NúñezNeurosurgery Unit, Hospital Universitario 12 de Octubre, Madrid, Spain.
Aurelio Hernández-LainNeuropathology Unit, Hospital Universitario 12 de Octubre, Madrid, Spain.
José Mazarico GallegoMedical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain.
Irene FerrerCNIO-H12O Clinical Cancer Research Unit, Fundación de Investigación Biomédica i+12 and CNIO, Madrid, Spain.
Rocío SuárezCNIO-H12O Clinical Cancer Research Unit, Fundación de Investigación Biomédica i+12 and CNIO, Madrid, Spain.
Eva M Garrido-MartínCNIO-H12O Clinical Cancer Research Unit, Fundación de Investigación Biomédica i+12 and CNIO, Madrid, Spain.
Luis Paz-AresMedical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain.
Celine DalmassoRadiation Oncology Department, Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France.
Elizabeth Cohen-Jonathan MoyalRadiation Oncology Department, Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France.
Aurore SiegfriedAnatomopathology Department, CHU Toulouse, IUCT-Oncopole, Toulouse, France.
Aisling HegartyEndocrine Oncology Research Group, RCSI University of Medicine and Health Sciences, Dublin, Ireland.
Stephen KeelanEndocrine Oncology Research Group, RCSI University of Medicine and Health Sciences, Dublin, Ireland.ORCID http://orcid.org/0000-0002-3632-5128
Damir VarešlijaEndocrine Oncology Research Group, RCSI University of Medicine and Health Sciences, Dublin, Ireland.ORCID http://orcid.org/0000-0003-1000-0357
Leonie S YoungEndocrine Oncology Research Group, RCSI University of Medicine and Health Sciences, Dublin, Ireland.ORCID http://orcid.org/0000-0002-4904-0367
Malte MohmeDepartment of Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID http://orcid.org/0000-0003-0627-9092
Yvonne GoyDepartment of Radiation Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Harriet WikmanDepartment of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.ORCID http://orcid.org/0000-0001-6862-0888
Jose Fernández-AlénDepartment of Neurosurgery, Hospital Universitario de La Princesa, Madrid, Spain.ORCID http://orcid.org/0000-0002-3321-983X
Guillermo BlascoDepartment of Neurosurgery, Hospital Universitario de La Princesa, Madrid, Spain.ORCID http://orcid.org/0000-0002-5342-7767
Lucía AlcázarDepartment of Neurosurgery, Hospital Universitario de La Princesa, Madrid, Spain.
Clara CabañuzDepartment of Pathology, Hospital Universitario La Paz, Madrid, Spain.
Sergei I GrivennikovCancer Prevention and Control Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
Andrada IanusChampalimaud Research, Champalimaud Centre for the Unknown, Lisbon, Portugal.ORCID http://orcid.org/0000-0001-9893-1724
Noam ShemeshChampalimaud Research, Champalimaud Centre for the Unknown, Lisbon, Portugal.
Claudia C FariaInstituto de Medicina Molecular João Lobo Antunes, Facultade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
Rebecca LeeFaculty of Biology Medicine and Health, The University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0003-2540-2009
Paul LoriganFaculty of Biology Medicine and Health, The University of Manchester, Manchester, UK.ORCID http://orcid.org/0000-0002-8875-2164
Emilie Le RhunDepartment of Neurology, University Hospital Zurich, Zurich, Switzerland.
Michael WellerDepartment of Neurology, University Hospital Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-1748-174X
Riccardo SoffiettiDivision of Neuro-Oncology, Department of Neuroscience Rita Levi Montalcini, University of Turin, Turin, Italy.
Luca BerteroDepartment of Medical Sciences, University of Turin, Turin, Italy.ORCID http://orcid.org/0000-0001-9887-7668
Umberto RicardiDepartment of Oncology, University of Turin, Turin, Italy.
Joaquim Bosch-BarreraDepartment of Medical Oncology, Catalan Institute of Oncology, Doctor Josep Trueta University Hospital, Girona, Spain.ORCID http://orcid.org/0000-0002-0893-7821
Elia SaisDepartment of Medical Oncology, Catalan Institute of Oncology, Doctor Josep Trueta University Hospital, Girona, Spain.
Eduard TeixidorDepartment of Medical Oncology, Catalan Institute of Oncology, Doctor Josep Trueta University Hospital, Girona, Spain.
Alejandro Hernández-MartínezDepartment of Medical Oncology, Catalan Institute of Oncology, Doctor Josep Trueta University Hospital, Girona, Spain.
Alfonso CalvoCIBERONC.
Javier AristuDepartment of Oncology, University Clinic of Navarra, Madrid, Spain.
Santiago M MartinDepartment of Oncology, University Clinic of Navarra, Pamplona, Spain.
Alvaro GonzalezDepartment of Biochemistry, University Clinic of Navarra, Pamplona, Spain.ORCID http://orcid.org/0000-0002-1423-273X
Omer AdlerDepartment of Pathology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Neta ErezDepartment of Pathology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
RENACER
Manuel ValienteBrain Metastasis Group, CNIO, Madrid, Spain. mvaliente@cnio.es.ORCID http://orcid.org/0000-0002-0647-7542
Spanish National Cancer Research Centre · ESHospital Universitario 12 De Octubre · ESInstituto Cajal · ESClinica Universidad de Navarra · ESHospital Universitario de La Princesa · ESInstitut Català d'Oncologia · ESUniversidad Complutense de Madrid · ESUniversität Hamburg · DEUniversity of Turin · ITChampalimaud Foundation · PTInstitut Claudius Regaud · FRTel Aviv University · ILUniversity Hospital of Zurich · CHUniversity of Manchester · GBCedars-Sinai Medical Center · USCentro de Investigación Biomédica en Red de Cáncer · ESCentro Nacional de Epidemiología · ESHospital Universitario La Paz · ESInstitut universitaire du cancer de Toulouse Oncopole · FRUniversitat de Girona · ES
Funding
The role of Interleukin 17RB signaling in colorectal cancer progressionR01CA227629 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI GRIVENNIKOV, SERGEI I · 2018 to 2022
$2.5MMechanisms of cytokine driven tumor elicited inflammation in colorectal cancerR01CA218133 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI GRIVENNIKOV, SERGEI I · 2018 to 2022
$2.4MNCI NIH HHS R01 CA218133NCI NIH HHS R01 CA227629
Abstract
Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.
Indexed as
Brain NeoplasmsMelanomaCranial IrradiationHumans
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.