ArticleNature medicine2025
Single-cell and spatial genomic landscape of non-small cell lung cancer brain metastases.
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Article in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50citing papers in PubMed
–field-weighted citation impact
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Who cites it
50 citing papers in PubMed.
- Artificial intelligence-powered spatial analysis of tumor microenvironment in patients with non-small cell lung cancer with acquired resistance to EGFR tyrosine kinase inhibitor.Journal for immunotherapy of cancer · 2025Trial
- Stereotactic Radiation Therapy for Lung Cancer Brain Metastases: Dose Optimization and Prognostic Prediction via Biologically Effective Dose-Based Empirical Dose-Response Modeling and Extreme Gradient Boosting-SHapley Additive Explanations Machine Learning.Advances in radiation oncology · 2026Article
- Clinical metastatic cancer from initiation to colonization: emerging challenges and breakthroughs.Oncogene · 2026Review
- Lung Cancer Brain Metastasis: Brain Microenvironmental Adaptation, Therapeutic Resistance and Translational Strategies.Cancer science · 2026Review
- Liver-originated selective autophagy of BTD by alectinib underlies concurrent hepatotoxicity and dermatotoxicity.Autophagy · 2026Article
- Pyroptosis-Amplified Decoy Nanovesicles Orchestrate Pyroptotic Antigen Explosion and Endogenous Immune Revitalization for Potentiating Tumour Immunotherapy.Journal of extracellular vesicles · 2026Article
- Neuro-immune crosstalk in lung cancer brain metastasis: mechanisms, therapeutic targets, and translational opportunities.Medical oncology (Northwood, London, England) · 2026Review
- Spatially resolved transcriptomics in human brain metastases identifies macrophage-tumor interactions associated with survival.iScience · 2026Article
- Astrocyte heterogeneity in brain metastases.Molecular oncology · 2026Review
- Mechanisms and therapeutic targets in distant metastasis of lung adenocarcinoma.Signal transduction and targeted therapy · 2026Article
- [Tumor Cell and Brain Microenvironment Interactions in Non-small Cell Lung Cancer Brain Metastasis: Mechanisms and Emerging Insights].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Multiscale systems modelling of communication networks in brain metastasis.Experimental & molecular medicine · 2026Review
- Roles of neutrophil extracellular traps in cancer immunotherapy resistance and therapeutic targeting.Biomarker research · 2026Review
- Future directions in the treatment of brain metastases: evaluating the role of cellular players in the tumour microenvironment.Acta neuropathologica · 2026Review
- Single-Cell Atlas of Renal Cell Carcinoma Brain Metastasis Uncovers Mechanisms of Immune Dysfunction and Resistance.bioRxiv : the preprint server for biology · 2026Article
- Astrocyte-driven immunosuppression in the brain tumor microenvironment.Nature immunology · 2026Review
- Coordinated Multicellular Immune Programs and Drug Targets Revealed by Single-Cell Analysis in Driver-Mutated NSCLC.International journal of molecular sciences · 2026Article
- Review
- From Neoantigens to Nanocarriers: Modern Methods and Modalities in Using Peptides for Cancer Vaccination.Biochemistry · 2026Review
- Charting the blueprint: a bibliometric analysis reveals future strategies in lung cancer targeted therapy (2003-2025).Journal of thoracic disease · 2026Article
Corrections and comments
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Authors and funding
50 authors.
Somnath Tagore *Division of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
Lindsay Caprio *Division of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0003-1370-8684
Amit Dipak Amin *Division of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-2613-2082
Kresimir Bestak *Institute for Computational Biomedicine, Faculty of Medicine, University Hospital Heidelberg and Heidelberg University, Heidelberg, Germany.ORCID http://orcid.org/0009-0009-8245-9846
Karan LuthriaDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-4392-9675
Edridge D'SouzaDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0003-4664-8163
Irving BarreraBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Johannes C MelmsDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-5410-6586
Sharon WuCaris Life Sciences, Phoenix, AZ, USA.
Sinan AbuzaidDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
Yiping WangDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
Viktoria JakubikovaDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
Peter KochDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
D Zack BrodtmanDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
Banpreet BawaDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
Sachin K DeshmukhCaris Life Sciences, Phoenix, AZ, USA.
Leon EbelDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0009-0007-2926-9619
Miguel A Ibarra-ArellanoInstitute for Computational Biomedicine, Faculty of Medicine, University Hospital Heidelberg and Heidelberg University, Heidelberg, Germany.ORCID http://orcid.org/0000-0001-8411-4854
Abhinav JaiswalDepartment of Dermatology, Immunology and Microbial Pathogenesis Program, Weill Cornell Medicine, New York, NY, USA.
Carino GurjaoDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
Jana BiermannDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
Neha ShaikhDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
Priyanka RamaradjDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-6349-7320
Yohanna GeorgisVagelos College of Physicians and Surgeons, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.
Galina G LagosLifespan Cancer Institute, The Warren Alpert Medical School of Brown University, Providence, RI, USA.ORCID http://orcid.org/0009-0003-6151-6545
Matthew I EhrlichDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
Patricia HoDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-4622-8188
Zachary H WalshDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
Meri RogavaDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
Michelle Garlin PolitisDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0003-2501-601X
Devanik BiswasVagelos College of Physicians and Surgeons, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0003-2714-5157
Azzurra CottarelliDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0003-4525-2028
Nikhil RizviDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
Catherine A ShuDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0003-0765-7665
Benjamin HerzbergDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
Niroshana AnandasabapathyDepartment of Dermatology, Immunology and Microbial Pathogenesis Program, Weill Cornell Medicine, New York, NY, USA.
George SledgeCaris Life Sciences, Phoenix, AZ, USA.
Emmanuel ZornColumbia Center for Translational Immunology, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0001-9985-8389
Peter CanollDepartment of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-7001-0226
Jeffrey N BruceDepartment of Neurological Surgery, New York Presbyterian/Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-6844-0286
Naiyer A RizviDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
Alison M TaylorVagelos College of Physicians and Surgeons, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0001-9341-535X
Anjali SaqiVagelos College of Physicians and Surgeons, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0003-3133-9886
Hanina HibshooshVagelos College of Physicians and Surgeons, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA.
Gary K SchwartzDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
Brian S HenickDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.ORCID http://orcid.org/0000-0003-2681-0805
Fei ChenBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2308-3649
Denis SchapiroInstitute for Computational Biomedicine, Faculty of Medicine, University Hospital Heidelberg and Heidelberg University, Heidelberg, Germany.
Parin ShahDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.
Benjamin IzarDivision of Hematology/Oncology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA. bi2175@cumc.columbia.edu.ORCID http://orcid.org/0000-0003-2379-6702
Funding
Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3MClinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0MStudying the evolution of drug resistance in prostate cancer at the single cell levelU54CA274506 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Peter Alan Sims · 2023 to 2026
$9.1MMedical Scientist Training ProgramT32GM145440 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI STEVEN L REINER · 2022 to 2026
$7.3MInterrogating unique DC adaptations to tissue to promote barrier immunity and toleranceR01AR080436 · NIAMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI Niroshana Anandasabapathy · 2022 to 2026
$3.5MMulti-cellular interactions defining the human brain metastatic nicheR01CA280414 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Benjamin Izar, Ashley Marie Laughney · 2023 to 2026
$2.8MMechanisms of liver metastasis and associated resistance to immunotherapyR37CA258829 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Benjamin Izar · 2021 to 2026
$2.6MNew mechanisms governing skin tissue residency memory T cellsR01AR083208 · NIAMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI Niroshana Anandasabapathy · 2024 to 2026
$2.1MThe role of the CD58:CD2 axis in cancer immune evasion and resistance to immunotherapyR01CA266446 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI FRANGIEH, CHRISTOPHER · 2022 to 2025
$2.0MTraining in Translational Immunology ResearchT32AI148099 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SYKES, MEGAN · 2020 to 2024
$1.4MChromosomal instability as a driver of non-small cell lung cancer immune evasion and brain metastasisF30CA281104 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Lindsay Anne Caprio · 2023 to 2026
$201kNCATS NIH HHS UL1 TR001873NCI NIH HHS F30 CA281104NCI NIH HHS P30 CA013696NCI NIH HHS R01 CA266446NCI NIH HHS R01 CA280414NCI NIH HHS R37 CA258829NCI NIH HHS U54 CA274506NIAID NIH HHS T32 AI148099NIAMS NIH HHS R01 AR080436NIAMS NIH HHS R01 AR083208NIGMS NIH HHS T32 GM145440
Abstract
Brain metastases frequently develop in patients with non-small cell lung cancer (NSCLC) and are a common cause of cancer-related deaths, yet our understanding of the underlying human biology is limited. Here we performed multimodal single-nucleus RNA and T cell receptor, single-cell spatial and whole-genome sequencing of brain metastases and primary tumors of patients with treatment-naive NSCLC. Chromosomal instability (CIN) is a distinguishing genomic feature of brain metastases compared with primary tumors, which we validated through integrated analysis of molecular profiling and clinical data in 4,869 independent patients, and a new cohort of 12,275 patients with NSCLC. Unbiased analyses revealed transcriptional neural-like programs that strongly enriched in cancer cells from brain metastases, including a recurring, CIN
Indexed as
Brain NeoplasmsCarcinoma, Non-Small-Cell LungLung NeoplasmsChromosomal InstabilityFemaleGene Expression Regulation, NeoplasticGenomicsHumansMaleSingle-Cell AnalysisTranscriptomeTumor Microenvironment
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