ArticleActa neuropathologica2021
Multi-omic molecular profiling reveals potentially targetable abnormalities shared across multiple histologies of brain metastasis.
Article in Acta neuropathologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Brain metastases: A Society for Neuro-Oncology (SNO) consensus review on current management and future directions.Neuro-oncology · 2022Guideline
- Ionizing Radiation Enhances Prognostically Significant Cellular Immunity Programs in the Brain Metastasis Microenvironment.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Single-Cell Atlas of Renal Cell Carcinoma Brain Metastasis Uncovers Mechanisms of Immune Dysfunction and Resistance.bioRxiv : the preprint server for biology · 2026Article
- The evolving landscape of brain metastasis: volume II.Trends in cancer · 2026Review
- A proteogenomic atlas of 1032 brain metastases identifies molecular subtypes, immune landscapes, and therapeutic vulnerabilities.Nature communications · 2026Article
- C/EBPβ-induced alternative splicing of RCAN1 generates a potent TCR-T target in mesenchymal glioblastoma.Cellular & molecular immunology · 2026Article
- The neuro-immune-vascular landscape of lung cancer brain metastasis: insights from organoid models.Frontiers in immunology · 2026Review
- IRS2 as a driver of brain metastasis in colorectal cancer: A potential target for novel therapeutic strategies.Neuro-oncology · 2025Article
- Metabolic adaptations of brain metastasis.Nature reviews. Cancer · 2025Review
- Review
- Genomic and immune profiling of breast cancer brain metastases.Acta neuropathologica communications · 2025Article
- Integrated analysis of molecular and clinical features associated with overall survival in melanoma patients with brain metastasis.Acta neuropathologica communications · 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
- The immune landscape in brain metastasis.Neuro-oncology · 2025Review
- Review
- Integrated analyses of multi-omic data derived from paired primary lung cancer and brain metastasis reveal the metabolic vulnerability as a novel therapeutic target.Genome medicine · 2024Article
- Astrocyte-induced Cdk5 expedites breast cancer brain metastasis by suppressing MHC-I expression to evade immune recognition.Nature cell biology · 2024Article
- Single-cell RNA sequencing reveals epithelial cells driving brain metastasis in lung adenocarcinoma.iScience · 2024Article
- Oxidative phosphorylation is a metabolic vulnerability of endocrine therapy and palbociclib resistant metastatic breast cancers.Nature communications · 2023Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
The deadly complication of brain metastasis (BM) is largely confined to a relatively narrow cross-section of systemic malignancies, suggesting a fundamental role for biological mechanisms shared across commonly brain metastatic tumor types. To identify and characterize such mechanisms, we performed genomic, transcriptional, and proteomic profiling using whole-exome sequencing, mRNA-seq, and reverse-phase protein array analysis in a cohort of the lung, breast, and renal cell carcinomas consisting of BM and patient-matched primary or extracranial metastatic tissues. While no specific genomic alterations were associated with BM, correlations with impaired cellular immunity, upregulated oxidative phosphorylation (OXPHOS), and canonical oncogenic signaling pathways including phosphoinositide 3-kinase (PI3K) signaling, were apparent across multiple tumor histologies. Multiplexed immunofluorescence analysis confirmed significant T cell depletion in BM, indicative of a fundamentally altered immune microenvironment. Moreover, functional studies using in vitro and in vivo modeling demonstrated heightened oxidative metabolism in BM along with sensitivity to OXPHOS inhibition in murine BM models and brain metastatic derivatives relative to isogenic parentals. These findings demonstrate that pathophysiological rewiring of oncogenic signaling, cellular metabolism, and immune microenvironment broadly characterizes BM. Further clarification of this biology will likely reveal promising targets for therapeutic development against BM arising from a broad variety of systemic cancers.
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Registered trials
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.