ArticleCell systems2022
Archetype tasks link intratumoral heterogeneity to plasticity and cancer hallmarks in small cell lung cancer.
Article in Cell systems, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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42 citing papers in PubMed, 56 citations in OpenAlex.
- CDState Resolves Malignant Cell Heterogeneity from Bulk Tumor RNA Sequencing Data.Cancer research · 2026Article
- ParTIpy: a scalable framework for archetypal analysis and Pareto task inference.Molecular systems 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
- KMT2D loss drives adeno-to-squamous transition and sensitizes TKI-resistant lung cancer to AURKA inhibition.Cell death and differentiation · 2026Article
- Mechanisms of resistance in small cell lung cancer.Chinese medical journal · 2026Review
- Recurrent intra-tumour heterogeneity is a hallmark of metastatic prostate cancer.Nature communications · 2026Article
- EMTscore infers divergent EMT pathways from omics data and enables rapid screening for EMT-associated gene sets.Bioinformatics (Oxford, England) · 2026Article
- Therapy as a State-Generator: Dynamic Phenotypic Landscapes and Adaptive Stress Circuits in Chemotherapy Resistance of Breast Cancer.Antioxidants (Basel, Switzerland) · 2026Review
- EMTscore infers divergent EMT pathways from omics data and enables rapid screening for correlated gene sets.bioRxiv : the preprint server for biology · 2026Article
- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
- Lack of caspase 8 directs neuronal progenitor-like reprogramming and small cell lung cancer progression.Nature communications · 2025Article
- Article
- YAP1 defines an emergent, plastic population of relapsed small cell lung cancer.bioRxiv : the preprint server for biology · 2025Article
- AAnet Resolves a Continuum of Spatially Localized Cell States to Unveil Intratumoral Heterogeneity.Cancer discovery · 2025Article
- Dynamic cell fate plasticity and tissue reintegration drive functional adult synovial joint regeneration after complete resection.Nature communications · 2025Article
- Intercellular signaling reinforces single-cell level phenotypic transitions and facilitates robust re-equilibrium of heterogeneous cancer cell populations.Cell communication and signaling : CCS · 2025Article
- Deep learning identifies heterogeneous subpopulations in breast cancer cell lines.npj biomedical innovations · 2025Article
- Challenges of small cell lung cancer heterogeneity and phenotypic plasticity.Nature reviews. Cancer · 2025Review
- Advancing therapeutics in small-cell lung cancer.Nature cancer · 2025Review
- Deciphering pre-existing and induced 3D genome architecture changes involved in constricted melanoma migration.iScience · 2025Article
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26 authors at 5 institutions in 1 country.
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Abstract
Small cell lung cancer (SCLC) tumors comprise heterogeneous mixtures of cell states, categorized into neuroendocrine (NE) and non-neuroendocrine (non-NE) transcriptional subtypes. NE to non-NE state transitions, fueled by plasticity, likely underlie adaptability to treatment and dismal survival rates. Here, we apply an archetypal analysis to model plasticity by recasting SCLC phenotypic heterogeneity through multi-task evolutionary theory. Cell line and tumor transcriptomics data fit well in a five-dimensional convex polytope whose vertices optimize tasks reminiscent of pulmonary NE cells, the SCLC normal counterparts. These tasks, supported by knowledge and experimental data, include proliferation, slithering, metabolism, secretion, and injury repair, reflecting cancer hallmarks. SCLC subtypes, either at the population or single-cell level, can be positioned in archetypal space by bulk or single-cell transcriptomics, respectively, and characterized as task specialists or multi-task generalists by the distance from archetype vertex signatures. In the archetype space, modeling single-cell plasticity as a Markovian process along an underlying state manifold indicates that task trade-offs, in response to microenvironmental perturbations or treatment, may drive cell plasticity. Stifling phenotypic transitions and plasticity may provide new targets for much-needed translational advances in SCLC. A record of this paper's Transparent Peer Review process is included in the supplemental information.
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