ArticleNature medicine2018
STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis.
Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT05689619 (A Phase 2 Randomized, Multicenter Trial on Silibinin To Prevent Intracranial Recurrence After Gross-Total Resection of Single Brain Metastasis From Non-Small Cell Lung Cancer or Breast Cancer), which is not on this map. Cited by 289 papers, 1 of them a synthesis that pooled it.
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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.
A Phase 2 Randomized, Multicenter Trial on Silibinin To Prevent Intracranial Recurrence After Gross-Total Resection of Single Brain Metastasis From Non-Small Cell Lung Cancer or Breast Cancer
Who cites it
289 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Brain metastases: A Society for Neuro-Oncology (SNO) consensus review on current management and future directions.Neuro-oncology · 2022Guideline
- Advances in the role of astrocytes in glioma progression and therapy.Acta pharmacologica Sinica · 2026Review
- Lung Cancer Brain Metastasis: Brain Microenvironmental Adaptation, Therapeutic Resistance and Translational Strategies.Cancer science · 2026Review
- Re-expression of MHC-I to treat CNS cancers.Oncotarget · 2026Review
- Addressing the Limits of Emx2 Therapy of Glioblastoma Multiforme by Transgene Insulation and Epigenetic Pharmacological Intervention.Biomedicines · 2026Article
- Neuro-immune crosstalk in lung cancer brain metastasis: mechanisms, therapeutic targets, and translational opportunities.Medical oncology (Northwood, London, England) · 2026Review
- Brain metastasis-associated fibroblasts shape the tumour microenvironment to enhance cancer cell invasion.Brain pathology (Zurich, Switzerland) · 2026Article
- Astrocyte heterogeneity in brain metastases.Molecular oncology · 2026Review
- The Origin of Cancer-Associated Fibroblasts (CAFs) in Brain Metastases: Seven Hypotheses and Current Evidence.Cancers · 2026Review
- Circular RNA dynamics in breast-to-brain metastatic cascade.BMC biology · 2026Article
- MIF-Induced CD74+ Microglia and Macrophages Promote Progression of Brain Metastasis and Are Clinically Relevant across Central Nervous System Disorders.Cancer research · 2026Article
- Spatial proteomic analysis in human Alzheimer's disease brains enables identification of microenvironment-dependent microglial cell states.Nature neuroscience · 2026Article
- Innate immune signaling and functions in astrocytes.Nature immunology · 2026Review
- Multiscale systems modelling of communication networks in brain metastasis.Experimental & molecular medicine · 2026Review
- Crosstalk In: crosstalk-aware inference of tumor microenvironment cell infiltration.Journal of translational medicine · 2026Article
- Molecular mechanisms and therapeutic targets in lung cancer-nerve crosstalk.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Single-nucleus multiomic atlas of ALS primary motor cortex nominates neuroprotective WDR49-expressing astrocytes.Research square · 2026Article
- Distinct immune landscapes characterize highly versus minimally invasive brain metastases.JCI insight · 2026Article
- Future directions in the treatment of brain metastases: evaluating the role of cellular players in the tumour microenvironment.Acta neuropathologica · 2026Review
- Astrocyte-associated immunosuppressive programs in brain tumors: a STAT3-centered perspective.Cancer metastasis reviews · 2026Review
229 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
26 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The brain microenvironment imposes a particularly intense selective pressure on metastasis-initiating cells, but successful metastases bypass this control through mechanisms that are poorly understood. Reactive astrocytes are key components of this microenvironment that confine brain metastasis without infiltrating the lesion. Here, we describe that brain metastatic cells induce and maintain the co-option of a pro-metastatic program driven by signal transducer and activator of transcription 3 (STAT3) in a subpopulation of reactive astrocytes surrounding metastatic lesions. These reactive astrocytes benefit metastatic cells by their modulatory effect on the innate and acquired immune system. In patients, active STAT3 in reactive astrocytes correlates with reduced survival from diagnosis of intracranial metastases. Blocking STAT3 signaling in reactive astrocytes reduces experimental brain metastasis from different primary tumor sources, even at advanced stages of colonization. We also show that a safe and orally bioavailable treatment that inhibits STAT3 exhibits significant antitumor effects in patients with advanced systemic disease that included brain metastasis. Responses to this therapy were notable in the central nervous system, where several complete responses were achieved. Given that brain metastasis causes substantial morbidity and mortality, our results identify a novel treatment for increasing survival in patients with secondary brain tumors.
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