ArticleMolecular oncology2022
Intrinsic and acquired drug resistance to LSD1 inhibitors in small cell lung cancer occurs through a TEAD4-driven transcriptional state.
Article in Molecular oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Reprogramming resistance in advanced lung cancer: epigenetic modulation to restore therapeutic vulnerability.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Epigenetics in lung cancer precision medicine: from bench to bedside-a narrative review.Translational lung cancer research · 2026Review
- Differential KEAP1/NRF2 mediated signaling widens the therapeutic window of redox-targeting drugs in SCLC therapy.Nature communications · 2026Article
- Potent and selective LSD1 inhibitor DC551040 reveals a promising combination therapy for AML with insight into epigenetic dysregulation.Signal transduction and targeted therapy · 2026Article
- Small Cell Lung Cancer Classification: Unraveling Heterogeneity to Enable Personalized Treatments.Cancer research · 2026Review
- Small cell lung cancer: from immunobiological mechanisms to clinical advances.Frontiers in immunology · 2026Review
- CoREST in pieces: Dismantling the CoREST complex for cancer therapy and beyond.Science advances · 2025Review
- Advancing therapeutics in small-cell lung cancer.Nature cancer · 2025Review
- Molecular basis and therapeutic implications of binary YAPOn/YAPOff cancer classes.The Biochemical journal · 2025Review
- Phase separation of RXRγ drives tumor chemoresistance and represents a therapeutic target for small-cell lung cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Actionable Driver Events in Small Cell Lung Cancer.International journal of molecular sciences · 2023Review
- A review of recent advances in the novel therapeutic targets and immunotherapy for lung cancer.Medical oncology (Northwood, London, England) · 2023Review
- A CRISPR Path to Finding Vulnerabilities and Solving Drug Resistance: Targeting the Diverse Cancer Landscape and Its Ecosystem.Advanced genetics (Hoboken, N.J.) · 2022Review
- Oncogenic roles of the lncRNA LINC00460 in human cancers.Cancer cell international · 2022Review
- A Four-Gene Prognostic Signature Based on the TEAD4 Differential Expression Predicts Overall Survival and Immune Microenvironment Estimation in Lung Adenocarcinoma.Frontiers in pharmacology · 2022Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small-cell lung cancer (SCLC) is a heterogeneous disease, consisting of intratumoral and intertumoral neuroendocrine (ASCL1 and/or NEUROD1), mesenchymal-like, and YAP-driven transcriptional states. Lysine-specific demethylase 1 (LSD1; also known as KDM1A) inhibitors have recently been progressed to clinical trials in SCLC based on a promising preclinical antitumor activity. A potential clinical limitation of LSD1 inhibitors is the heterogeneous drug responses that have been observed in SCLC cell lines and patient-derived models. Based on these observations, we studied molecular and transcriptional signatures that predict patient response to this class of drug. Employing SCLC patient-derived transcriptional signatures, we define that SCLC cell lines sensitive to LSD1 inhibitors are enriched in neuroendocrine transcriptional markers, whereas cell lines enriched in a mesenchymal-like transcriptional program demonstrate intrinsic resistance to LSD1 inhibitors. We have identified a reversible, adaptive resistance mechanism to LSD1 inhibitors through epigenetic reprogramming to a TEAD4-driven mesenchymal-like state. Our data suggest that only a segment of SCLC patients, with a defined neuroendocrine differentiation state, will likely benefit from LSD1 inhibitors. It provides novel evidence for the selection of a TEAD4-driven mesenchymal-like subpopulation resistant to LSD1 inhibitors in SCLC patients that may require effective drug combinations to sustain effective clinical responses.
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