ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2026
YAP1 Defines an Emergent, Plastic Population of Relapsed SCLC.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
- CyTOF-based profiling of circulating tumor cells predicts aggressiveness and therapy response in SCLC liquid biopsies at a personalized level.bioRxiv : the preprint server for biology · 2025Article
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Abstract
introductionSCLC is an aggressive neuroendocrine malignancy characterized by rapid onset of chemoresistance and poor clinical outcomes. Transcriptional heterogeneity among treatment-naive SCLC tumors underlies four transcriptional subtypes, each with distinct clinical vulnerabilities. Though previously hypothesized to delineate a distinct subtype, expression of YAP1 is largely absent from treatment-naive, pure SCLC.
methodsMethods: To characterize relapsed SCLC, circulating tumor DNA, circulating tumor cells, and core needle biopsies from patients with SCLC and preclinical models following resistance to standard-of-care therapies were analyzed.
resultsIn contrast to treatment-naive SCLC, these analyses reveal an emergent YAP1-positive cell population that coincides with treatment resistance. These YAP1-positive cells exhibit characteristics of drug-tolerant persister cells, including senescence, stemness, and plasticity, as YAP1-positive cells largely abandon features characteristic of SCLC to adopt those of large cell neuroendocrine carcinoma. As a result of this SCLC-like to large cell neuroendocrine carcinoma-like evolution, YAP1-positive cells lack several clinically relevant SCLC surface targets (i.e., DLL3, SEZ6) but are enriched for others (i.e., B7-H3, TROP2)
conclusionsWe propose a model where YAP1-expressing cells emerge with SCLC treatment resistance and characterize a tenacious subpopulation capable of diverging from the treatment-naive lineage and adopting features to evade therapeutic response.
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