ArticleProceedings of the National Academy of Sciences of the United States of America2024
EHMT2-mediated transcriptional reprogramming drives neuroendocrine transformation in non-small cell lung cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Histological transformation in lung cancer: a single-arm meta-analysis and systematic review.BMC cancer · 2026Pooled it
- Traditional Chinese medicine monotherapy in extensive-stage small cell lung cancer: A Case Report.Medicine · 2026Article
- Spatiotemporal heterogeneity of neutrophil extracellular traps in hepatocellular carcinoma microenvironment and targeted therapy progress.Journal of translational medicine · 2026Review
- Targeting EHMT2 inhibition in glioblastoma: effects on tumor progression and STAT3 signaling.Translational cancer research · 2026Article
- Loss of EHMT2 enhances NK cell-driven anti-tumor immunity through TGF-β1 suppression.EMBO molecular medicine · 2026Article
- Advanced and underlying therapeutic strategies in transformed small cell lung cancer.Frontiers in medicine · 2026Review
- Lung cancer organoids for functional precision oncology: from disease modeling to clinical decision support.Frontiers in oncology · 2026Review
- Integrated methylome analysis identifies an epigenetically silenced tumor suppressor RASA4 in small cell lung cancer.Communications biology · 2025Article
- Molecular mechanisms and clinical insights in transformed small cell lung cancer: a narrative review.Translational lung cancer research · 2025Review
- Molecular basis and therapeutic implications of binary YAPOn/YAPOff cancer classes.The Biochemical journal · 2025Review
- The inhibitory effect of Osthole on A549 lung adenocarcinoma cells and its biomarker.Scientific reports · 2025Article
- Review
- EHMT2-mediated R-loop formation promotes the malignant progression of prostate cancer via activating Aurora B.Clinical and translational medicine · 2025Article
- Histologic transformation after targeted therapy resistance in driver gene-positive NSCLC: mechanisms and therapeutic challenges.Therapeutic advances in medical oncology · 2025Review
- Mechanism exploration and model construction for small cell transformation in EGFR-mutant lung adenocarcinomas.Signal transduction and targeted therapy · 2024Article
- Neuroendocrine transdifferentiation in human cancer: molecular mechanisms and therapeutic targets.MedComm · 2024Review
- Overcoming drug resistance through extracellular vesicle-based drug delivery system in cancer treatment.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Personalized care for patients with EGFR-mutant nonsmall cell lung cancer: Navigating early to advanced disease management.CA: a cancer journal for cliniciansReview
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Authors and funding
16 authors.
Funding
Abstract
The transformation of lung adenocarcinoma to small cell lung cancer (SCLC) is a recognized resistance mechanism and a hindrance to therapies using epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). The paucity of pretranslational/posttranslational clinical samples limits the deeper understanding of resistance mechanisms and the exploration of effective therapeutic strategies. Here, we developed preclinical neuroendocrine (NE) transformation models. Next, we identified a transcriptional reprogramming mechanism that drives resistance to erlotinib in NE transformation cell lines and cell-derived xenograft mice. We observed the enhanced expression of genes involved in the EHMT2 and WNT/β-catenin pathways. In addition, we demonstrated that EHMT2 increases methylation of the SFRP1 promoter region to reduce SFRP1 expression, followed by activation of the WNT/β-catenin pathway and TKI-mediated NE transformation. Notably, the similar expression alterations of EHMT2 and SFRP1 were observed in transformed SCLC samples obtained from clinical patients. Importantly, suppression of EHMT2 with selective inhibitors restored the sensitivity of NE transformation cell lines to erlotinib and delayed resistance in cell-derived xenograft mice. We identify a transcriptional reprogramming process in NE transformation and provide a potential therapeutic target for overcoming resistance to erlotinib.
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