ArticlePLoS computational biology2019
Systems-level network modeling of Small Cell Lung Cancer subtypes identifies master regulators and destabilizers.
Article in PLoS computational biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed.
- Integrating molecular subtypes, genomics and functional dependencies to identify context-specific therapeutic vulnerabilities in small cell lung cancer.Biomarker research · 2026Review
- FOXA1 drives chemoresistance through activating Wnt pathway in small cell lung cancer.Translational lung cancer research · 2026Article
- Mechanisms of resistance in small cell lung cancer.Chinese medical journal · 2026Review
- UHRF1 drives subtype-independent aggressiveness and immune evasion in small cell lung cancer through PRC2 interactions.iScience · 2026Article
- LSD1 inhibitor, TAS1440, disrupts INSM1-LSD1 complex activating tumor-suppressive pathways via transcriptional reprogramming in neuroendocrine SCLC.Nature communications · 2026Article
- Subtype-specific dependencies and therapeutic opportunities in small cell lung cancer.Science advances · 2026Review
- Small Cell Lung Cancer Classification: Unraveling Heterogeneity to Enable Personalized Treatments.Cancer research · 2026Review
- Unmasking biomarkers in small cell lung cancer: implication for precision oncology.Frontiers in oncology · 2026Review
- Article
- Intercellular signaling reinforces single-cell level phenotypic transitions and facilitates robust re-equilibrium of heterogeneous cancer cell populations.Cell communication and signaling : CCS · 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
- Systems Biology of the Cancer Cell.Annual review of biomedical engineering · 2025Review
- Molecular heterogeneity of small cell lung cancer and new therapeutic possibilities: a narrative review of the literature.Translational lung cancer research · 2025Review
- Molecular Subtypes and Targeted Therapeutic Strategies in Small Cell Lung Cancer: Advances, Challenges, and Future Perspectives.Molecules (Basel, Switzerland) · 2025Review
- Intratumoral heterogeneity and potential treatment strategies in small cell lung cancer.Frontiers in oncology · 2025Review
- Genomic Profiling of Extensive Stage Small-Cell Lung Cancer Patients Identifies Molecular Factors Associated with Survival.Lung Cancer (Auckland, N.Z.) · 2025Article
- Differential NEUROD1, ASCL1, and POU2F3 Expression Defines Molecular Subsets of Bladder Small Cell/Neuroendocrine Carcinoma With Prognostic Implications.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2024Article
- Small cell lung cancer profiling: an updated synthesis of subtypes, vulnerabilities, and plasticity.Trends in cancer · 2024Review
- Molecular subtypes and prognostic factors of lung large cell neuroendocrine carcinoma.Translational lung cancer research · 2024Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors.
Funding
Abstract
Adopting a systems approach, we devise a general workflow to define actionable subtypes in human cancers. Applied to small cell lung cancer (SCLC), the workflow identifies four subtypes based on global gene expression patterns and ontologies. Three correspond to known subtypes (SCLC-A, SCLC-N, and SCLC-Y), while the fourth is a previously undescribed ASCL1+ neuroendocrine variant (NEv2, or SCLC-A2). Tumor deconvolution with subtype gene signatures shows that all of the subtypes are detectable in varying proportions in human and mouse tumors. To understand how multiple stable subtypes can arise within a tumor, we infer a network of transcription factors and develop BooleaBayes, a minimally-constrained Boolean rule-fitting approach. In silico perturbations of the network identify master regulators and destabilizers of its attractors. Specific to NEv2, BooleaBayes predicts ELF3 and NR0B1 as master regulators of the subtype, and TCF3 as a master destabilizer. Since the four subtypes exhibit differential drug sensitivity, with NEv2 consistently least sensitive, these findings may lead to actionable therapeutic strategies that consider SCLC intratumoral heterogeneity. Our systems-level approach should generalize to other cancer types.
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