ArticleCancers2019
Inhibition of Histone Demethylases LSD1 and UTX Regulates ERα Signaling in Breast Cancer.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- The impact of margins in laryngeal cancer patients treated with transoral laser microsurgery: a systematic review and meta-analysis.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2024Pooled it
- Heat up, silence on: IDO1 gene silencing in THP-1-derived dendritic cells triggered by magnetic hyperthermia.Cancer immunology, immunotherapy : CII · 2025Article
- Discovery of novel dual-target inhibitors of LSD1/EGFR for non-small cell lung cancer therapy.Acta pharmacologica Sinica · 2025Article
- Efficacy and safety analysis of atezolizumab continuation beyond progression in extensive-stage small cell lung cancer.Clinical and experimental medicine · 2025Article
- H4K20me3, H3K4me2 and H3K9me2 mediate the effect of ER on prognosis in breast cancer.Epigenetics · 2024Article
- The emerging roles of histone demethylases in cancers.Cancer metastasis reviews · 2024Review
- KDM5 family as therapeutic targets in breast cancer: Pathogenesis and therapeutic opportunities and challenges.Molecular cancer · 2024Review
- Review
- LSD1 inhibitors for cancer treatment: Focus on multi-target agents and compounds in clinical trials.Frontiers in pharmacology · 2023Review
- Lysine-specific demethylase 1 deficiency modifies aldosterone synthesis in a sex-specific manner.The Journal of endocrinology · 2023Article
- Epigenetic modulation of antitumor immunity and immunotherapy response in breast cancer: biological mechanisms and clinical implications.Frontiers in immunology · 2023Review
- Proteomic characterization of post-translational modifications in drug discovery.Acta pharmacologica Sinica · 2022Review
- The epigenetics of breast cancer - Opportunities for diagnostics, risk stratification and therapy.Epigenetics · 2022Article
- The paradigm of drug resistance in cancer: an epigenetic perspective.Bioscience reports · 2022Review
- Epigenetic Determinants of Racial Disparity in Breast Cancer: Looking beyond Genetic Alterations.Cancers · 2022Review
- Epigenetic Factors as Etiological Agents, Diagnostic Markers, and Therapeutic Targets for Luminal Breast Cancer.Biomedicines · 2022Review
- A state-of-the-art review on LSD1 and its inhibitors in breast cancer: Molecular mechanisms and therapeutic significance.Frontiers in pharmacology · 2022Review
- Antitumor Effect of Demethylzeylasteral (T-96) on Triple-Negative Breast Cancer via LSD1-Mediate Epigenetic Mechanisms.Analytical cellular pathology (Amsterdam) · 2022Article
- Control of Breast Cancer Pathogenesis by Histone Methylation and the Hairless Histone Demethylase.Endocrinology · 2021Review
- Epigenetic Regulation of Breast Cancer Stem Cells Contributing to Carcinogenesis and Therapeutic Implications.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
22 authors at 7 institutions in 5 countries.
Funding
Abstract
In breast cancer, Lysine-specific demethylase-1 (LSD1) and other lysine demethylases (KDMs), such as Lysine-specific demethylase 6A also known as Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), are co-expressed and co-localize with estrogen receptors (ERs), suggesting the potential use of hybrid (epi)molecules to target histone methylation and therefore regulate/redirect hormone receptor signaling. Here, we report on the biological activity of a dual-KDM inhibitor (MC3324), obtained by coupling the chemical properties of tranylcypromine, a known LSD1 inhibitor, with the 2OG competitive moiety developed for JmjC inhibition. MC3324 displays unique features not exhibited by the single moieties and well-characterized mono-pharmacological inhibitors. Inhibiting LSD1 and UTX, MC3324 induces significant growth arrest and apoptosis in hormone-responsive breast cancer model accompanied by a robust increase in H3K4me2 and H3K27me3. MC3324 down-regulates ERα in breast cancer at both transcriptional and non-transcriptional levels, mimicking the action of a selective endocrine receptor disruptor. MC3324 alters the histone methylation of ERα-regulated promoters, thereby affecting the transcription of genes involved in cell surveillance, hormone response, and death. MC3324 reduces cell proliferation in ex vivo breast cancers, as well as in breast models with acquired resistance to endocrine therapies. Similarly, MC3324 displays tumor-selective potential in vivo, in both xenograft mice and chicken embryo models, with no toxicity and good oral efficacy. This epigenetic multi-target approach is effective and may overcome potential mechanism(s) of resistance in breast cancer.
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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.