ArticleEMBO molecular medicine2022
Promoters of ASCL1- and NEUROD1-dependent genes are specific targets of lurbinectedin in SCLC cells.
Article in EMBO molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Pharmacokinetics and Safety of Lurbinectedin Administrated with Itraconazole in Cancer Patients: A Drug-Drug Interaction Study.Marine drugs · 2024Trial
- A MYC family switch: L-MYC drives and maintains neuroendocrine lineage programs in prostate cancer.Neoplasia (New York, N.Y.) · 2026Article
- A MYC Family Switch: L-MYC Drives and Maintains Neuroendocrine Lineage Programs in Prostate Cancer.bioRxiv : the preprint server for biology · 2025Article
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- Article
- Unveiling the Mechanism of Lurbinectedin's Action and Its Potential in Combination Therapies in Small Cell Lung Cancer.Molecular cancer therapeutics · 2025Review
- Transcriptomic analysis of transformed small-cell lung cancer from EGFR-mutated lung adenocarcinoma reveals distinct subgroups and precision therapy opportunities.Biomarker research · 2025Article
- Molecular Subtypes and Targeted Therapeutic Strategies in Small Cell Lung Cancer: Advances, Challenges, and Future Perspectives.Molecules (Basel, Switzerland) · 2025Review
- Lethal co-expression intolerance underlies the mutually exclusive expression of ASCL1 and NEUROD1 in SCLC cells.NPJ precision oncology · 2025Article
- Targeting FOXP1 phase separation in small cell lung cancer mechanisms of chemotherapy resistance.Communications biology · 2025Article
- Defined cellular reprogramming of androgen receptor-active prostate cancer to neuroendocrine prostate cancer.bioRxiv : the preprint server for biology · 2025Article
- Genomic alterations and transcriptional phenotypes in circulating free DNA and matched metastatic tumor.Genome medicine · 2025Article
- Pan-inhibition of super-enhancer-driven oncogenic transcription by next-generation synthetic ecteinascidins yields potent anti-cancer activity.Nature communications · 2025Article
- Neuroendocrine transdifferentiation in human cancer: molecular mechanisms and therapeutic targets.MedComm · 2024Review
- Small cell lung cancer profiling: an updated synthesis of subtypes, vulnerabilities, and plasticity.Trends in cancer · 2024Review
- Prognostic Implications of Small Cell Lung Cancer Transcriptional Subtyping for CNS Metastases.JCO precision oncology · 2024Article
- Trabectedin derails transcription-coupled nucleotide excision repair to induce DNA breaks in highly transcribed genes.Nature communications · 2024Article
- Actionable Driver Events in Small Cell Lung Cancer.International journal of molecular sciences · 2023Review
- NeuroD1-GPX4 signaling leads to ferroptosis resistance in hepatocellular carcinoma.PLoS genetics · 2023Article
- Potent molecular-targeted therapies for gastro-entero-pancreatic neuroendocrine carcinoma.Cancer metastasis reviews · 2023Review
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small-Cell Lung Cancer (SCLC) is an aggressive neuroendocrine malignancy with a poor prognosis. Here, we focus on the neuroendocrine SCLC subtypes, SCLC-A and SCLC-N, whose transcription addiction was driven by ASCL1 and NEUROD1 transcription factors which target E-box motifs to activate up to 40% of total genes, the promoters of which are maintained in a steadily open chromatin environment according to ATAC and H3K27Ac signatures. This leverage is used by the marine agent lurbinectedin, which preferentially targets the CpG islands located downstream of the transcription start site, thus arresting elongating RNAPII and promoting its degradation. This abrogates the expression of ASCL1 and NEUROD1 and of their dependent genes, such as BCL2, INSM1, MYC, and AURKA, which are responsible for relevant SCLC tumorigenic properties such as inhibition of apoptosis and cell survival, as well as for a part of its neuroendocrine features. In summary, we show how the transcription addiction of these cells becomes their Achilles's heel, and how this is effectively exploited by lurbinectedin as a novel SCLC therapeutic endeavor.
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