ArticleCell reports. Medicine2024
Microenvironment shapes small-cell lung cancer neuroendocrine states and presents therapeutic opportunities.
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Article in Cell reports. Medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37citing papers in PubMed
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Who cites it
37 citing papers in PubMed.
- C-X-C Motif Chemokine Receptor 4 (CXCR4)-Targeted Biologically Guided Proton Spatially Fractionated Radiotherapy for Bulky Limited-Stage Small Cell Lung Cancer.Precision radiation oncology · 2026Article
- Blockade of Tumor-Intrinsic TGFβ Signaling Drives Hyperprogression in Small Cell Lung Cancer.Cancer discovery · 2026Article
- Proteomic Profiling Identifies CLDN3 as a Tumor-Selective Therapeutic Target in Small Cell Lung Cancer.bioRxiv : the preprint server for biology · 2026Article
- Single-Cell and Spatial Transcriptomics Reframe the Immunosuppressive Microenvironment of Neuroendocrine Neoplasms.Cancers · 2026Review
- Cancer-associated fibroblasts and tertiary lymphoid structure orchestrate the spatial architecture of tumor immunity.Journal of hematology & oncology · 2026Review
- Research progress on immune microenvironment and biomarkers of small cell lung cancer.Journal of thoracic disease · 2026Review
- Bidirectional coupling among EMT, AXL-RB1 signaling and lineage switch drives resistance to osimertinib and worse clinical outcomes in NSCLC.bioRxiv : the preprint server for biology · 2026Article
- A new era of precision diagnosis and treatment for lung cancer: artificial intelligence-driven multimodal data integration and clinical applications.Cell death & disease · 2026Review
- Spatial multi-omics unveils the monoclonal origin, neuroendocrine plasticity, and microenvironment niches in combined small-cell lung cancer.Cell reports. Medicine · 2026Article
- Targeting TPX2-dependent lineage plasticity by CDK4/6 inhibition reverses therapy resistance in neuroendocrine bladder carcinoma.Cell reports. Medicine · 2026Article
- Single-cell spatial transcriptomics reveals tumor microenvironment heterogeneity in primary and lymph node-metastatic small cell lung cancer.Cell reports. Medicine · 2026Article
- Article
- UHRF1 drives subtype-independent aggressiveness and immune evasion in small cell lung cancer through PRC2 interactions.iScience · 2026Article
- Heterogeneity and plasticity of cancer-associated fibroblasts.Nature cancer · 2026Review
- Multi-omics reveals key molecular and cellular features of advanced small cell lung cancers associated with distinct therapeutic opportunities.Genome medicine · 2026Article
- Small Cell Lung Cancer Classification: Unraveling Heterogeneity to Enable Personalized Treatments.Cancer research · 2026Review
- Multiomic characterization of small cell lung cancer: Real-world insights into therapeutic opportunities.Cancer · 2026Article
- Spatial transcriptomics reveals molecular heterogeneity and subtype-specific therapeutic targets in small cell lung cancer.NPJ precision oncology · 2026Article
- Reframing small cell lung cancer: therapeutic lessons from hematologic malignancies.Frontiers in oncology · 2026Review
- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
Corrections and comments
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Authors and funding
58 authors.
Parth DesaiDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Department of Medical Oncology, Fox Chase Cancer Center, Temple University Hospital and Lewis Katz School of Medicine, Philadelphia, PA, USA.
Nobuyuki TakahashiDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA; Department of Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Rajesh KumarDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Samantha NicholsDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Justin MalinDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Allison HuntWomen's Health Integrated Research Center, Inova Health System, Falls Church, VA, USA.
Christopher SchultzDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Yingying CaoCancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Desiree TilloCCR Collaborative Bioinformatics, Resource, Office of Science and Technology Resources, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Darryl NousomeCCR Collaborative Bioinformatics, Resource, Office of Science and Technology Resources, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Lakshya ChauhanCenter for Biosystems Science and Engineering, Indian Institute of Science, Bangalore, India.
Linda SciutoDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Kimberly JordanDepartment of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Vinodh RajapakseDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Mayank TandonCCR Collaborative Bioinformatics, Resource, Office of Science and Technology Resources, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Delphine LissaLaboratory of Human Carcinogenesis, Center for Cancer Research National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Yang ZhangDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Suresh KumarDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Lorinc PongorHCEMM Cancer Genomics and Epigenetics Research Group, Szeged, Hungary.
Abhay SinghCenter for Biosystems Science and Engineering, Indian Institute of Science, Bangalore, India.
Brett SchroderDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Ajit Kumar SharmaDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Tiangen ChangCancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Rasa VilimasDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Danielle PinkiertDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Chante GrahamDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Donna ButcherMolecular Histopathology Laboratory, Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Andrew WarnerMolecular Histopathology Laboratory, Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Robin SebastianDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Mimi MahonPain and Palliative care services, National Institutes of Health Clinical Center, Bethesda, MD, USA.
Karen BakerPain and Palliative care services, National Institutes of Health Clinical Center, Bethesda, MD, USA.
Jennifer ChengPain and Palliative care services, National Institutes of Health Clinical Center, Bethesda, MD, USA.
Ann BergerPain and Palliative care services, National Institutes of Health Clinical Center, Bethesda, MD, USA.
Ross LakeLaboratory of Genitourinary cancer Pathogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Melissa AbelDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Manan KrishnamurthyDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
George ChrisafisDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Peter FitzgeraldCCR Collaborative Bioinformatics, Resource, Office of Science and Technology Resources, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Micheal NirulaDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Shubhank GoyalDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Devon AtkinsonCenter for Advanced Preclinical Research, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Nicholas W BatemanThe Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA.
Tamara AbulezThe Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, USA.
Govind NairNational Institute of Neurological Disorders and Stroke, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Andrea ApoloGenitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Udayan GuhaThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Baktiar KarimMolecular Histopathology Laboratory, Laboratory Animal Sciences Program, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Rajaa El MeskiniCenter for Advanced Preclinical Research, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Zoe Weaver OhlerCenter for Advanced Preclinical Research, Frederick National Laboratory for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Mohit Kumar JollyCenter for Biosystems Science and Engineering, Indian Institute of Science, Bangalore, India.
Alejandro SchafferCancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Eytan RuppinCancer Data Science Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
David KleinerLaboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Markku MiettinenLaboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
G Tom BrownLaboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Stephen HewittLaboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Thomas ConradsWomen's Health Integrated Research Center, Inova Health System, Falls Church, VA, USA.
Anish ThomasDevelopmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: anish.thomas@nih.gov.
Funding
CCR Collaborative Bioinformatics ResourceZICBC011532 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MALIK, MARIAM · 2013 to 2025
$33.7MImmunohistochemical and genomic analysis of tumorsZIABC011427 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MIETTINEN, MARKKU · 2012 to 2025
$24.0MCCR Genomics CoreZICBC011623 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI CONNER, ELIZABETH · 2015 to 2025
$20.5MExperimental Pathology Laboratory (EPL)ZICBC011638 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HEWITT, STEPHEN · 2015 to 2025
$16.6MPostmortem PathologyZICBC010685 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KLEINER, DAVID ERWIN · 2009 to 2025
$14.3MDevelopment of Novel Preclinical Animal Models - CAPR InfrastructureZIGBC011735 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SHARAN, SHYAM · 2016 to 2025
$4.3MNINDS Quantitative MRI Core FacilityZICNS009438 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI NAIR, GOVIND · 2022 to 2025
$4.3MAbstract
Small-cell lung cancer (SCLC) is the most fatal form of lung cancer. Intratumoral heterogeneity, marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell states, defines SCLC, but the cell-extrinsic drivers of SCLC plasticity are poorly understood. To map the landscape of SCLC tumor microenvironment (TME), we apply spatially resolved transcriptomics and quantitative mass spectrometry-based proteomics to metastatic SCLC tumors obtained via rapid autopsy. The phenotype and overall composition of non-malignant cells in the TME exhibit substantial variability, closely mirroring the tumor phenotype, suggesting TME-driven reprogramming of NE cell states. We identify cancer-associated fibroblasts (CAFs) as a crucial element of SCLC TME heterogeneity, contributing to immune exclusion, and predicting exceptionally poor prognosis. Our work provides a comprehensive map of SCLC tumor and TME ecosystems, emphasizing their pivotal role in SCLC's adaptable nature, opening possibilities for reprogramming the TME-tumor communications that shape SCLC tumor states.
Indexed as
Lung NeoplasmsSmall Cell Lung CarcinomaTumor MicroenvironmentCancer-Associated FibroblastsFemaleHumansMaleNeuroendocrine CellsNeuroendocrine TumorsPrognosiscancer-associated fibroblastsintercellular communicationrapid research autopsysmall-cell lung cancerspatial transcriptomicstumor heterogeneitytumor microenvironment
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