ArticleNature cancer2020
Single-cell analyses reveal increased intratumoral heterogeneity after the onset of therapy resistance in small-cell lung cancer.
Article in Nature cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05257551 (Tempus SCLC Observational Study), which is not on this map. Cited by 251 papers.
What it found
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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.
Tempus SCLC Observational Study: A Tissue and Longitudinal Circulating Tumor DNA (ctDNA) Biomarker Profiling Study of Patients With Small Cell Lung Cancer (SCLC) Using Comprehensive Next-Generation Sequencing (NGS) Assays
Who cites it
251 citing papers in PubMed, 361 citations in OpenAlex.
- Spatial Transcriptomics Analysis of Ewing Sarcoma.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Mitochondrial NADP(H)-dependent de novo dTMP biosynthesis counteracts the cytotoxicity of PARP inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Uncovering pan-cancer signatures of chemoresistance.Genome medicine · 2026Article
- PAX5 modulates vascularization and contributes to neuroendocrine lineage transition during carcinoma progression.The Journal of clinical investigation · 2026Article
- Patient-Derived Organoid and Single-Cell Multiomics Reveal Evolution Driven by CEACAM6/KRT19-Mediated Heterogeneity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- YAP1 Defines an Emergent, Plastic Population of Relapsed SCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- FOXA1 drives chemoresistance through activating Wnt pathway in small cell lung cancer.Translational lung cancer research · 2026Article
- [Expert Consensus on Immunotherapy for Extensive-stage Small Cell Lung Cancer Based on Molecular Subtyping].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Loss of the USP22 deubiquitylase confers resistance to chemotherapy in small cell lung cancer.Nature communications · 2026Article
- 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 transcriptomics reveals heterogeneity and immune microenvironment in lymphatic metastasis of head and neck squamous cell carcinoma.Genes and immunity · 2026Article
- Decoding drug-responsive cell subpopulations in triple-negative breast cancer using single-cell multiomics.iScience · 2026Article
- The Impact of Targeting TRAF2 and NCK-Interacting Protein Kinase on Antitumor Effect and Tumor Immune Environment in c-MYC-High SCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- Circulating Tumor Cells Predict Response to the DLL3-Targeting Bispecific Antibody Tarlatamab.Cancer discovery · 2026Article
- Multi-omics analysis identified serumJournal of thoracic disease · 2026Article
- Differential KEAP1/NRF2 mediated signaling widens the therapeutic window of redox-targeting drugs in SCLC therapy.Nature communications · 2026Article
- Unraveling the intricacies of small cell lung cancer: FAK splicing variants as a new feature and therapeutic vulnerability of small cell lung cancer.MedScience · 2026Article
- Epithelial plasticity shapes intratumoral heterogeneity and cell lineages in early-stage lung cancer.Science advances · 2026Article
- Single-cell profiling of tumor lineage plasticity and the immune microenvironment in transformed small cell lung cancer.Journal of translational medicine · 2026Article
191 more citing papers are in PubMed but not listed here.
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Authors and funding
25 authors at 3 institutions in 1 country.
Funding
Abstract
The natural history of small cell lung cancer (SCLC) includes rapid evolution from chemosensitivity to chemoresistance, although mechanisms underlying this evolution remain obscure due to scarcity of post-relapse tissue samples. We generated circulating tumor cell (CTC)-derived xenografts (CDXs) from SCLC patients to study intratumoral heterogeneity (ITH) via single-cell RNAseq of chemo-sensitive and -resistant CDXs and patient CTCs. We found globally increased ITH including heterogeneous expression of therapeutic targets and potential resistance pathways, such as EMT, between cellular subpopulations following treatment-resistance. Similarly, serial profiling of patient CTCs directly from blood confirmed increased ITH post-relapse. These data suggest that treatment-resistance in SCLC is characterized by coexisting subpopulations of cells with heterogeneous gene expression leading to multiple, concurrent resistance mechanisms. These findings emphasize the need for clinical efforts to focus on rational combination therapies for treatment-naïve SCLC tumors to maximize initial responses and counteract the emergence of ITH and diverse resistance mechanisms.
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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.