Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (764 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Compounds that inhibit histone deacetylases. This class of drugs may influence gene expression by increasing the level of acetylated histones in specific chromatin domains.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Deacetylase Inhibitors, Histone; Inhibitors, Histone Deacetylase; HDAC Inhibitor; Inhibitor, HDAC; HDAC Inhibitors; Inhibitors, HDAC; Histone Deacetylase Inhibitor; Deacetylase Inhibitor, Histone.
Where it fits in the MeSH classification
- Broader topics
- Enzyme Inhibitors
Related concepts
- Histone Deacetylases
- Histones
- Chromatin
Research landscape
PubMed indexes 13,493 records tagged with the MeSH heading “Histone Deacetylase Inhibitors” (counts retrieved 2026-10-29). 3,403 of them (25.2%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 6,929 records.
Reviews account for 2,203 records (16.3%) and meta-analyses for 14. Randomized controlled trials number 51 (0.4%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 16 |
| 2000-2009 | 3,145 |
| 2010-2019 | 6,929 |
| 2020 onward | 3,403 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 2,203 | 16.3% |
| Meta-analyses | 14 | 0.1% |
| Randomized controlled trials | 51 | 0.4% |
Method: PubMed query "Histone Deacetylase Inhibitors"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in pharmacology
Drug evidence builds in layers: laboratory pharmacology describes how a compound acts, pharmacokinetic studies describe how the body handles it, and randomized trials test whether it helps and what harms it causes. Post-marketing surveillance and observational studies reveal rarer adverse effects but cannot prove causation. This page is educational and is not a recommendation to start, stop or change any medicine; decisions about treatment belong with a qualified clinician.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Advances in targeting histone deacetylase for treatment of solid tumors | 2024 | Review article Design not recorded in structured metadata | 139 | cc by PMID 38822399 · DOI · PMC11143662 |
| Lactylation of HDAC1 Confers Resistance to Ferroptosis in Colorectal Cancer | 2025 | Research article Design not recorded in structured metadata | 87 | cc by PMID 39888307 · DOI · PMC11947995 |
| Sintilimab (anti-PD-1 antibody) plus chidamide (histone deacetylase inhibitor) in relapsed or refractory extranodal natural killer T-cell lymphoma (SCENT): a phase Ib/II study | 2024 | Research article Design not recorded in structured metadata | 41 | cc by PMID 38755119 · DOI · PMC11099117 |
| Transient histone deacetylase inhibition induces cellular memory of gene expression and 3D genome folding | 2026 | Research article Design not recorded in structured metadata | 17 | cc by PMID 41639407 · DOI · PMC12900649 |
Advances in targeting histone deacetylase for treatment of solid tumors [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Histone deacetylase (HDAC) serves as a critical molecular regulator in the pathobiology of various malignancies and have garnered attention as a viable target for therapeutic intervention.
- Closing excerpt
- Despite these challenges, we believe that advancements in HDACi research and improvements in combination therapies will pave the way or lead to a broad and hopeful future in the treatment of solid tumors.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (197 words)
Histone deacetylase (HDAC) serves as a critical molecular regulator in the pathobiology of various malignancies and have garnered attention as a viable target for therapeutic intervention. A variety of HDAC inhibitors (HDACis) have been developed to target HDACs. Many preclinical studies have conclusively demonstrated the antitumor effects of HDACis, whether used as monotherapy or in combination treatments. On this basis, researchers have conducted various clinical studies to evaluate the potential of selective and pan-HDACis in clinical settings. In our work, we extensively summarized and organized current clinical trials, providing a comprehensive overview of the current clinical advancements in targeting HDAC therapy. Furthermore, we engaged in discussions about several clinical trials that did not yield positive outcomes, analyzing the factors that led to their lack of anticipated therapeutic effectiveness. Apart from the experimental design factors, issues such as toxicological side effects, tumor heterogeneity, and unexpected off-target effects also contributed to these less-than-expected results. These challenges have naturally become significant barriers to the application of HDACis. Despite these challenges, we believe that advancements in HDACi research and improvements in combination therapies will pave the way or lead to a broad and hopeful future in the treatment of solid tumors.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 38822399 · DOI · PMC11143662
Lactylation of HDAC1 Confers Resistance to Ferroptosis in Colorectal Cancer [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Colorectal cancer (CRC) is highly resistant to ferroptosis, which hinders the application of anti-ferroptosis therapy.
- Closing excerpt
- In conclusion, the research reveals that HDACi decreases HDAC1K412 lactylation to sensitize CRC to ferroptosis and that the combination of HDACi and ferroptosis inducers can be a promising therapeutic strategy for CRC.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (181 words)
Colorectal cancer (CRC) is highly resistant to ferroptosis, which hinders the application of anti-ferroptosis therapy. Through drug screening, it is found that histone deacetylase inhibitor (HDACi) significantly sensitized CRC to ferroptosis. The combination of HDACi and ferroptosis inducers synergically suppresses CRC growth both in vivo and in vitro. Mechanically, HDACi reduces ferroptosis suppressor protein (FSP1) by promoting its mRNA degradation. Specifically, it is confirmed that HDACi specifically targets HDAC1 and promotes the H3K27ac modification of fat mass- and obesity-associated gene (FTO) and AlkB Homolog 5, RNA Demethylase (ALKBH5), which results in significant activation of FTO and ALKBH5. The activation of FTO and ALKBH5 reduces N6-methyladenosine (m6A) modification on FSP1 mRNA, leading to its degradation. Crucially, lactylation of HDAC1K412 is essential for ferroptosis regulation. Both Vorinostat (SAHA) and Trichostatin A (TSA) notably diminish HDAC1K412 lactylation in comparison to other HDAC1 inhibitors, exhibiting a consistent trend of increasing susceptibility to ferroptosis. In conclusion, the research reveals that HDACi decreases HDAC1K412 lactylation to sensitize CRC to ferroptosis and that the combination of HDACi and ferroptosis inducers can be a promising therapeutic strategy for CRC.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 39888307 · DOI · PMC11947995
Sintilimab (anti-PD-1 antibody) plus chidamide (histone deacetylase inhibitor) in relapsed or refractory extranodal natural killer T-cell lymphoma (SCENT): a phase Ib/II study [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma (RR-ENKTL), however, the complete response (CR) rate and the duration of response (DOR) need to be improved.
- Closing excerpt
- It is a promising therapeutic option for this population.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (237 words)
Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma (RR-ENKTL), however, the complete response (CR) rate and the duration of response (DOR) need to be improved. This phase 1b/2 study investigated the safety and efficacy of sintilimab, a fully human anti-PD-1 antibody, plus chidamide, an oral subtype-selective histone deacetylase inhibitor in 38 patients with RR-ENKTL. Expected objective response rate (ORR) of combination treatment was 80%. Patients received escalating doses of chidamide, administered concomitantly with fixed-dose sintilimab in 21-days cycles up to 12 months. No dose-limiting events were observed, RP2D of chidamide was 30 mg twice a week. Twenty-nine patients were enrolled in phase 2. In the intention-to-treat population (n = 37), overall response rate was 59.5% with a complete remission rate of 48.6%. The median DOR, progression-free survival (PFS), and overall survival (OS) were 25.3, 23.2, and 32.9 months, respectively. The most common grade 3 or higher treatment-emergent adverse events (AEs) were neutropenia (28.9%) and thrombocytopenia (10.5%), immune-related AEs were reported in 18 (47.3%) patients. Exploratory biomarker assessment suggested that a combination of dynamic plasma ctDNA and EBV-DNA played a vital prognostic role. STAT3 mutation shows an unfavorable prognosis. Although outcome of anticipate ORR was not achieved, sintilimab plus chidamide was shown to have a manageable safety profile and yielded encouraging CR rate and DOR in RR-ENKTL for the first time. It is a promising therapeutic option for this population.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 38755119 · DOI · PMC11099117
Transient histone deacetylase inhibition induces cellular memory of gene expression and 3D genome folding [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Epigenetic memory enables the propagation of gene expression patterns following transient stimuli.
- Closing excerpt
- These results demonstrate how cells can record transient stresses in their genome architecture, thereby enabling an enhanced response to subsequent perturbations.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (149 words)
Epigenetic memory enables the propagation of gene expression patterns following transient stimuli. Although three-dimensional chromatin organization is emerging as a key regulator of genome function, it is unknown whether it contributes to cellular memory. Here we establish that acute perturbation of the epigenome can induce cellular memory of gene expression in mouse embryonic stem cells. We uncover how a pulse of histone deacetylase inhibition translates to changes in transcription, histone modifications and genome folding. While most epigenomic and transcriptional changes are initially reversed once the perturbation is removed, some loci remain transcriptionally deregulated and genome architecture partially maintains its perturbed conformation. Consequently, a second pulse of transient hyperacetylation induces stronger memory of transcriptional deregulation. Using ultradeep Micro-C, we associate memory of gene expression with repressive Polycomb-mediated chromatin topology. These results demonstrate how cells can record transient stresses in their genome architecture, thereby enabling an enhanced response to subsequent perturbations.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41639407 · DOI · PMC12900649
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article HDACs and HDAC Inhibitors in Cancer Development and Therapy [5]
- Research article Histone Deacetylase Inhibitors as Anticancer Drugs [6]
- Research article Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents [7]
- Research article Epigenetic regulation in human cancer: the potential role of epi-drug in cancer therapy [8]
- Research article Histone Deacetylases (HDACs): Evolution, Specificity, Role in Transcriptional Complexes, and Pharmacological Actionability [9]
- Research article Epigenetic modulation and understanding of HDAC inhibitors in cancer therapy [10]
References
- Shi MQ, Xu Y, Fu X, Pan DS, Lu XP, Xiao Y, et al.. Advances in targeting histone deacetylase for treatment of solid tumors. . 2024. PMID 38822399 · DOI · PMC11143662
- Yang Z, Su W, Zhang Q, Niu L, Feng B, Zhang Y, et al.. Lactylation of HDAC1 Confers Resistance to Ferroptosis in Colorectal Cancer. . 2025. PMID 39888307 · DOI · PMC11947995
- Gao Y, He H, Li X, Zhang L, Xu W, Feng R, et al.. Sintilimab (anti-PD-1 antibody) plus chidamide (histone deacetylase inhibitor) in relapsed or refractory extranodal natural killer T-cell lymphoma (SCENT): a phase Ib/II study. . 2024. PMID 38755119 · DOI · PMC11099117
- Paldi F, Szalay MF, Dufau S, Di Stefano M, Reboul H, Jost D, et al.. Transient histone deacetylase inhibition induces cellular memory of gene expression and 3D genome folding. . 2026. PMID 41639407 · DOI · PMC12900649
- Li Y, Seto E. HDACs and HDAC Inhibitors in Cancer Development and Therapy. Cold Spring Harb Perspect Med. 2016. PMID 27599530 · DOI · PMC5046688
- Eckschlager T, Plch J, Stiborova M, Hrabeta J. Histone Deacetylase Inhibitors as Anticancer Drugs. Int J Mol Sci. 2017. PMID 28671573 · DOI · PMC5535906
- Mottamal M, Zheng S, Huang TL, Wang G. Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents. Molecules. 2015. PMID 25738536 · DOI · PMC4372801
- Lu Y, Chan YT, Tan HY, Li S, Wang N, Feng Y. Epigenetic regulation in human cancer: the potential role of epi-drug in cancer therapy. Mol Cancer. 2020. PMID 32340605 · DOI · PMC7184703
- Milazzo G, Mercatelli D, Di Muzio G, Triboli L, De Rosa P, Perini G, et al.. Histone Deacetylases (HDACs): Evolution, Specificity, Role in Transcriptional Complexes, and Pharmacological Actionability. Genes (Basel). 2020. PMID 32429325 · DOI · PMC7288346
- Ramaiah MJ, Tangutur AD, Manyam RR. Epigenetic modulation and understanding of HDAC inhibitors in cancer therapy. Life Sci. 2021. PMID 33872660 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.