ArticleAging2020
The LSD1 inhibitor iadademstat (ORY-1001) targets SOX2-driven breast cancer stem cells: a potential epigenetic therapy in luminal-B and HER2-positive breast cancer subtypes.
Article in Aging, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- A systematic review of progress toward unlocking the power of epigenetics in breast cancer: latest updates and perspectives.Frontiers in pharmacology · 2025Pooled it
- Emerging Targeted and Multimodal Therapeutic Strategies in Breast Cancer: A Comprehensive Review.Breast cancer (Dove Medical Press) · 2026Review
- Upregulation of Sox2 Following Saracatinib Treatment Contributes to a Resistant Phenotype in Colorectal Cancer Cells under Growth Factor-Supplemented Conditions.Oncology research · 2026Article
- Histone lysine demethylases in breast cancer: molecular mechanisms, biological functions, and therapeutic intervention.Molecular cancer · 2025Review
- CtBP1-LSD1 complex drives ErbB2 activation via H3K9me2 demethylation in DRGs during paclitaxel-induced neuropathic pain.Cell biology and toxicology · 2025Article
- CoREST in pieces: Dismantling the CoREST complex for cancer therapy and beyond.Science advances · 2025Review
- Mechanistic insights into novel cyano-pyrimidine pendant chalcone derivatives as LSD1 inhibitors by docking, ADMET, MM/GBSA, and molecular dynamics simulation.Biochemistry and biophysics reports · 2025Article
- Unraveling the immune mechanisms and therapeutic targets in lung adenosquamous transformation.Frontiers in immunology · 2025Review
- Epigenetic regulation espeically histone modifications in breast cancer: A viable and emerging targeted therapeutic strategy.Journal of Cancer · 2025Review
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Informed by Cancer Stem Cells of Solid Tumors: Advances in Treatments Targeting Tumor-Promoting Factors and Pathways.International journal of molecular sciences · 2024Review
- Lysine demethylase LSD1 is associated with stemness in EBV-positive B cell lymphoma.Scientific reports · 2024Article
- Histone modifications in drug-resistant cancers: From a cancer stem cell and immune evasion perspective.Experimental & molecular medicine · 2023Review
- Epigenetic Regulation in Breast Cancer: Insights on Epidrugs.Epigenomes · 2023Review
- Viscosalactone B, a natural LSD1 inhibitor, inhibits proliferation in vitro and in vivo against prostate cancer cells.Investigational new drugs · 2023Article
- Targeting Breast Cancer Stem Cells.International journal of biological sciences · 2023Review
- Chemical modulation ofWellcome open research · 2023Article
- Aberrant expression of KDM1A inhibits ferroptosis of lung cancer cells through up-regulating c-Myc.Scientific reports · 2022Article
- Targeting Histone Epigenetic Modifications and DNA Damage Responses in Synthetic Lethality Strategies in Cancer?Cancers · 2022Article
- The epigenetics of breast cancer - Opportunities for diagnostics, risk stratification and therapy.Epigenetics · 2022Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SOX2 is a core pluripotency-associated transcription factor causally related to cancer initiation, aggressiveness, and drug resistance by driving the self-renewal and seeding capacity of cancer stem cells (CSC). Here, we tested the ability of the clinically proven inhibitor of the lysine-specific demethylase 1 (LSD1/KDM1A) iadademstat (ORY-100) to target SOX2-driven CSC in breast cancer. Iadademstat blocked CSC-driven mammosphere formation in breast cancer cell lines that are dependent on SOX2 expression to maintain their CSC phenotype. Iadademstat prevented the activation of an LSD1-targeted stemness-specific SOX2 enhancer in CSC-enriched 3-dimensional spheroids. Using high-throughput transcriptional data available from the METABRIC dataset, high expression of SOX2 was significantly more common in luminal-B and HER2-enriched subtypes according to PAM50 classifier and in IntClust1 (high proliferating luminal-B) and IntClust 5 (luminal-B and HER2-amplified) according to integrative clustering. Iadademstat significantly reduced mammospheres formation by CSC-like cells from a multidrug-resistant luminal-B breast cancer patient-derived xenograft but not of those from a treatment-naïve luminal-A patient. Iadademstat reduced the expression of SOX2 in luminal-B but not in luminal-A mammospheres, likely indicating a selective targeting of SOX2-driven CSC. The therapeutic relevance of targeting SOX2-driven breast CSC suggests the potential clinical use of iadademstat as an epigenetic therapy in luminal-B and HER2-positive subtypes.
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Registered trials
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.