ArticleThe Journal of investigative dermatology2021
The HDAC Inhibitor Domatinostat Promotes Cell-Cycle Arrest, Induces Apoptosis, and Increases Immunogenicity of Merkel Cell Carcinoma Cells.
Article in The Journal of investigative dermatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 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
- Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma.Journal for immunotherapy of cancer · 2021Trial
- Review
- The role of B2M in cancer immunotherapy resistance: function, resistance mechanism, and reversal strategies.Frontiers in immunology · 2025Review
- Histones deacetylases in the epidermis: structure, functions and therapeutic implications.Frontiers in epigenetics and epigenomics · 2025Review
- Advancing Treatment Options for Merkel Cell Carcinoma: A Review of Tumor-Targeted Therapies.International journal of molecular sciences · 2024Review
- Apoptosis, a Metabolic "Head-to-Head" between Tumor and T Cells: Implications for Immunotherapy.Cells · 2024Review
- Merkel cell carcinoma: updates in tumor biology, emerging therapies, and preclinical models.Frontiers in oncology · 2024Review
- Unraveling the landscape of non-melanoma skin cancer through single-cell RNA sequencing technology.Frontiers in oncology · 2024Review
- The HDAC inhibitor domatinostat induces type I interferon α in Merkel cell carcinoma by HES1 repression.Journal of cancer research and clinical oncology · 2023Article
- An Investigation of Structure-Activity Relationships and Cell Death Mechanisms of the Marine Alkaloids Discorhabdins in Merkel Cell Carcinoma Cells.Marine drugs · 2023Article
- Super-enhancers complexes zoom in transcription in cancer.Journal of experimental & clinical cancer research : CR · 2023Review
- Single-cell dissection of Merkel cell carcinoma heterogeneity unveils transcriptomic plasticity and therapeutic vulnerabilities.Cell reports. Medicine · 2023Article
- Epigenetic Regulation in Breast Cancer: Insights on Epidrugs.Epigenomes · 2023Review
- Curcuphenol possesses an unusual histone deacetylase enhancing activity that counters immune escape in metastatic tumours.Frontiers in pharmacology · 2023Article
- Review
- Merkel Cell Carcinoma Sensitivity to EZH2 Inhibition Is Mediated by SIX1 Derepression.The Journal of investigative dermatology · 2022Article
- HDAC Class I Inhibitor Domatinostat Preferentially Targets Glioma Stem Cells over Their Differentiated Progeny.International journal of molecular sciences · 2022Article
- Genomic evidence suggests that cutaneous neuroendocrine carcinomas can arise from squamous dysplastic precursors.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2022Article
- The Role of Histone Post-Translational Modifications in Merkel Cell Carcinoma.Frontiers in oncology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Merkel cell carcinoma (MCC) is a rare, highly aggressive skin cancer for which immune modulation by immune checkpoint inhibitors shows remarkable response rates. However, primary or secondary resistance to immunotherapy prevents benefits in a significant proportion of patients. For MCC, one immune escape mechanism is insufficient for recognition by T cells owing to the downregulation of major histocompatibility complex I surface expression. Histone deacetylase inhibitors have been demonstrated to epigenetically reverse the low major histocompatibility complex I expression caused by the downregulation of the antigen-processing machinery. Domatinostat, an orally available small-molecule inhibitor targeting histone deacetylase class I, is currently in clinical evaluation to overcome resistance to immunotherapy. In this study, we present preclinical data on domatinostat's efficacy and mode of action in MCC. Single-cell RNA sequencing revealed a distinct gene expression signature of antigen processing and presentation, cell-cycle arrest, and execution phase of apoptosis on treatment. Accordingly, functional assays showed that domatinostat induced G2M arrest and apoptosis. In the surviving cells, antigen-processing machinery component gene transcription and translation were upregulated, consequently resulting in increased major histocompatibility complex I surface expression. Altogether, domatinostat not only exerts direct antitumoral effects but also restores HLA class I surface expression on MCC cells, therefore, restoring surviving MCC cells' susceptibility to recognition and elimination by cognate cytotoxic T cells.
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What Socratic holds
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 Socratic graph.