ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Inhibition of LSD1 with Bomedemstat Sensitizes Small Cell Lung Cancer to Immune Checkpoint Blockade and T-Cell Killing.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 110 citations in OpenAlex.
- DNA hypomethylation identifying clinical benefit subgroup of small-cell lung cancer: multi-omics analysis of a phase II trial with durvalumab plus olaparib as maintenance therapy.Journal for immunotherapy of cancer · 2026Trial
- NOTCH1 reverses immune suppression in small cell lung cancer through reactivation of STING.The Journal of clinical investigation · 2025Trial
- Molecular classification and biomarkers of outcome with immunotherapy in extensive-stage small-cell lung cancer: analyses of the CASPIAN phase 3 study.Molecular cancer · 2024Trial
- Clinical Benefit From Immunotherapy in Patients With SCLC Is Associated With Tumor Capacity for Antigen Presentation.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2023Trial
- The dual roles of lysine-specific demethylase 1 (KDM1A/LSD1) in the modulation of tumor immune microenvironment and its inhibitors in colorectal cancer.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Epigenetics in lung cancer precision medicine: from bench to bedside-a narrative review.Translational lung cancer research · 2026Review
- RNA-binding protein RALYL-mediated BCL11B RNA stability promotes immune escape in small cell lung cancer through transcriptional activation of BUB3.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Cancer stem cell plasticity: mechanisms, immune microenvironment crosstalk, and therapeutic implications.Journal of hematology & oncology · 2026Review
- Histone modifications across cancers: mechanisms, therapy and clinical translation.Molecular cancer · 2026Review
- Research progress on immune microenvironment and biomarkers of small cell lung cancer.Journal of thoracic disease · 2026Review
- Targeting lysine-specific demethylase 1 inhibits melanoma metastasis via the NF2-Hippo-YAP pathway.Cell death & disease · 2026Article
- TAF1 Suppresses MHC-I Expression and Correlates with Poor Immunotherapy Response in Small Cell Lung Cancer.Biomedicines · 2026Article
- UHRF1 drives subtype-independent aggressiveness and immune evasion in small cell lung cancer through PRC2 interactions.iScience · 2026Article
- Differential KEAP1/NRF2 mediated signaling widens the therapeutic window of redox-targeting drugs in SCLC therapy.Nature communications · 2026Article
- The novel tertiary amine LSD1 inhibitor 596 inhibits endometrial cancer through the mTOR signal transduction pathway.Translational oncology · 2026Article
- Subtype-specific dependencies and therapeutic opportunities in small cell lung cancer.Science advances · 2026Review
- Review
- LSD1 Inhibition Induces MHC-I and Dendritic Cell Activation to Promote Antitumor Immunity in Head and Neck Squamous Cell Carcinoma.Cancer research · 2026Article
- Therapeutic targeting of chromatin alterations in leukemia and solid tumors.International journal of cancer · 2026Review
- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
26 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
purposeThe addition of immune checkpoint blockade (ICB) to platinum/etoposide chemotherapy changed the standard of care for small cell lung cancer (SCLC) treatment. However, ICB addition only modestly improved clinical outcomes, likely reflecting the high prevalence of an immunologically "cold" tumor microenvironment in SCLC, despite high mutational burden. Nevertheless, some patients clearly benefit from ICB and recent reports have associated clinical responses to ICB in SCLC with (i) decreased neuroendocrine characteristics and (ii) activation of NOTCH signaling. We previously showed that inhibition of the lysine-specific demethylase 1a (LSD1) demethylase activates NOTCH and suppresses neuroendocrine features of SCLC, leading us to investigate whether LSD1 inhibition would enhance the response to PD-1 inhibition in SCLC. EXPERIMENTAL
designWe employed a syngeneic immunocompetent model of SCLC, derived from a genetically engineered mouse model harboring Rb1/Trp53 inactivation, to investigate combining the LSD1 inhibitor bomedemstat with anti-PD-1 therapy. In vivo experiments were complemented by cell-based studies in murine and human models.
resultsBomedemstat potentiated responses to PD-1 inhibition in a syngeneic model of SCLC, resulting in increased CD8+ T-cell infiltration and strong tumor growth inhibition. Bomedemstat increased MHC class I expression in mouse SCLC tumor cells in vivo and augmented MHC-I induction by IFNγ and increased killing by tumor-specific T cells in cell culture.
conclusionsLSD1 inhibition increased MHC-I expression and enhanced responses to PD-1 inhibition in vivo, supporting a new clinical trial to combine bomedemstat with standard-of-care PD-1 axis inhibition in SCLC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.