ArticleNature communications2022
Heterogeneity of neuroendocrine transcriptional states in metastatic small cell lung cancers and patient-derived models.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 100 citations in OpenAlex.
- NOTCH1 reverses immune suppression in small cell lung cancer through reactivation of STING.The Journal of clinical investigation · 2025Trial
- Plasma nucleosome profiling reports on tumor burden and molecular subtypes in small cell lung cancer.The Journal of clinical investigation · 2026Article
- Article
- PAX5 modulates vascularization and contributes to neuroendocrine lineage transition during carcinoma progression.The Journal of clinical investigation · 2026Article
- Integrating molecular subtypes, genomics and functional dependencies to identify context-specific therapeutic vulnerabilities in small cell lung cancer.Biomarker research · 2026Review
- Spindle Assembly Checkpoint Competency Determines Sensitivity to KIF18A Inhibition in Small Cell Lung Cancer.Cancer research communications · 2026Article
- DLL3-Targeted Strategies in Advanced Prostate Cancer: Current Evidence and Future Perspectives.Drugs · 2026Review
- Blockade of Tumor-Intrinsic TGFβ Signaling Drives Hyperprogression in Small Cell Lung Cancer.Cancer discovery · 2026Article
- Automated detection and characterization of small cell lung cancer liver metastasis on computed tomography.Diagnostic and interventional radiology (Ankara, Turkey) · 2026Article
- Immunohistochemical profiling of small cell lung cancer reveals subtype heterogeneity and a tuft cell-like subtype characterized by LRMP and TRPM5.Virchows Archiv : an international journal of pathology · 2026Article
- Mechanisms of resistance in small cell lung cancer.Chinese medical journal · 2026Review
- Treatment monitoring by biomarker analysis in a Phase I dose-expansion study of AZD2811 for relapsed/refractory small-cell lung cancer.British journal of cancer · 2026Article
- Single-cell spatial transcriptomics reveals tumor microenvironment heterogeneity in primary and lymph node-metastatic small cell lung cancer.Cell reports. Medicine · 2026Article
- Transcription Factor Subtype Governs Response and Resistance to DLL3-Directed T-Cell Engagement in Small Cell Lung Cancer.bioRxiv : the preprint server for biology · 2026Article
- SMARCA4 Loss Promotes Late-Stage Tumor Progression in Nonneuroendocrine Small Cell Lung Cancer.Molecular cancer research : MCR · 2026Article
- Lineage plasticity: a new dilemma in lung cancer treatment.Molecular biology reports · 2026Review
- Pathobiology and clinical significance of malignant pleural effusions.EMBO molecular medicine · 2026Review
- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
- Unmasking biomarkers in small cell lung cancer: implication for precision oncology.Frontiers in oncology · 2026Review
- Reframing small cell lung cancer: therapeutic lessons from hematologic malignancies.Frontiers in oncology · 2026Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
Molecular subtypes of small cell lung cancer (SCLC) defined by the expression of key transcription regulators have recently been proposed in cell lines and limited number of primary tumors. The clinical and biological implications of neuroendocrine (NE) subtypes in metastatic SCLC, and the extent to which they vary within and between patient tumors and in patient-derived models is not known. We integrate histology, transcriptome, exome, and treatment outcomes of SCLC from a range of metastatic sites, revealing complex intra- and intertumoral heterogeneity of NE differentiation. Transcriptomic analysis confirms previously described subtypes based on ASCL1, NEUROD1, POU2F3, YAP1, and ATOH1 expression, and reveal a clinical subtype with hybrid NE and non-NE phenotypes, marked by chemotherapy-resistance and exceedingly poor outcomes. NE tumors are more likely to have RB1, NOTCH, and chromatin modifier gene mutations, upregulation of DNA damage response genes, and are more likely to respond to replication stress targeted therapies. In contrast, patients preferentially benefited from immunotherapy if their tumors were non-NE. Transcriptional phenotypes strongly skew towards the NE state in patient-derived model systems, an observation that was confirmed in paired patient-matched tumors and xenografts. We provide a framework that unifies transcriptomic and genomic dimensions of metastatic SCLC. The marked differences in transcriptional diversity between patient tumors and model systems are likely to have implications in development of novel therapeutic agents.
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