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Histone deacetylases tighten the packaging of DNA so that genes are switched off. Drugs that block them loosen the packaging and can wake up genes that make lymphoma cells stop growing or die.
Histone deacetylases remove acetyl groups from lysines on histones and on non-histone proteins such as p53, HSP90 and tubulin, condensing chromatin and repressing transcription. Class I (HDAC1, 2, 3, 8) and class II (HDAC4 to 7, 9, 10) enzymes are the targets of approved inhibitors: vorinostat and romidepsin in cutaneous T-cell lymphoma, belinostat and romidepsin in peripheral T-cell lymphoma, and panobinostat (US approval withdrawn) in multiple myeloma. Responses are modest as single agents in solid tumours; combinations with immunotherapy and with hypomethylating agents are under study.
In plain words · Histone deacetylases tighten the packaging of DNA so that genes are switched off. Drugs that block them loosen the packaging and can wake up genes that make lymphoma cells stop growing or die.
Histone deacetylases tighten the packaging of DNA so that genes are switched off. Drugs that block them loosen the packaging and can wake up genes that make lymphoma cells stop growing or die.
Inhibition causes histone hyperacetylation, cell-cycle arrest via p21 induction, apoptosis and reduced angiogenesis; class-related toxicities are fatigue, thrombocytopenia, diarrhoea and QT prolongation.
3 products aim at Histone deacetylases (HDAC): small molecules. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
Broadly expressed or essential: HPA lists HDAC3 among essential proteins and finds the RNA at low tissue specificity; the 5 medicines aimed at it (Romidepsin, Belinostat, Vorinostat and more) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA HDAC1: RNA low tissue specificity; high antibody staining in 19 normal tissues; highest cancer staining thyroid cancer (4 of 4 high). HPA HDAC2: RNA low tissue specificity; high antibody staining in 38 normal tissues; highest cancer staining colorectal cancer (12 of 12 high). HPA HDAC3: RNA low tissue specificity; high antibody staining in 4 normal tissues; highest cancer staining head and neck cancer (1 of 4 high). HPA HDAC6: RNA low tissue specificity; high antibody staining in 3 normal tissues; highest cancer staining liver cancer (1 of 11 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Lymphoma, Multiple myeloma); Open Targets associates it with 5 specific cancer types at or above 0.5 (primary cutaneous T-cell non-Hodgkin lymphoma, plasma cell myeloma, T-cell non-Hodgkin lymphoma, peripheral T-cell lymphoma, not otherwise specified, mature T-cell and NK-cell non-Hodgkin lymphoma). (Rule 7 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas HDAC1 tissue; Human Protein Atlas HDAC2 tissue; Human Protein Atlas HDAC3 tissue; Human Protein Atlas HDAC6 tissue; Open Targets ENSG00000116478 associations; Open Targets ENSG00000196591 associations
Inhibition causes histone hyperacetylation, cell-cycle arrest via p21 induction, apoptosis and reduced angiogenesis; class-related toxicities are fatigue, thrombocytopenia, diarrhoea and QT prolongation.
RNA: low tissue specificity, detected in all normal tissues.
Medium: Breast, Endometrium, Kidney, Liver, Lung, Lymph node, Nasopharynx, Ovary.
Medium only: renal cancer.
HPA HDAC1 tissue · HPA HDAC1 pathology · HPA protein class: FDA approved drug targets
RNA: low tissue specificity, detected in all normal tissues.
Medium: Breast, Rectum, Seminal vesicle, Small intestine, Thyroid gland, Vagina.
HPA HDAC2 tissue · HPA HDAC2 pathology · HPA protein class: FDA approved drug targets
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adrenal gland, Appendix, Breast, Caudate, Cervix, Colon, Duodenum, Endometrium.
Medium only: breast cancer, carcinoid, endometrial cancer, lung cancer.
HPA HDAC3 tissue · HPA HDAC3 pathology · HPA protein class: Essential proteins, FDA approved drug targets
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adrenal gland, Appendix, Bone marrow, Cerebellum, Cerebral cortex, Cervix, Colon, Duodenum.
Medium only: breast cancer, carcinoid, cervical cancer, colorectal cancer.
HPA HDAC6 tissue · HPA HDAC6 pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
ABT-301 is an experimental small-molecule drug from Anbogen Therapeutics in phase 2 trials for colorectal cancer, aimed at Histone deacetylases (HDAC).
Resminostat is an oral drug of the HDAC inhibitor class, proposed for advanced mycosis fungoides and Sézary syndrome, two cutaneous T-cell lymphomas. Europe's medicines committee said no to it in May 2025, so it is not authorised.
Vorinostat (Zolinza) was the first drug of its kind, a capsule that loosens the chemical packaging of DNA. It treats the skin disease of cutaneous T-cell lymphoma after two other treatments have failed.
Query for this target: (TITLE:"Histone deacetylases" OR ABSTRACT:"Histone deacetylases" OR TITLE:"HDAC" OR ABSTRACT:"HDAC" OR TITLE:"HDAC1" OR ABSTRACT:"HDAC1" OR TITLE:"HDAC2" OR ABSTRACT:"HDAC2" OR TITLE:"HDAC3" OR ABSTRACT:"HDAC3" OR TITLE:"HDAC6" OR ABSTRACT:"HDAC6") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Histone deacetylases (HDAC), not a curated reading list.
Shares Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome and the tag epigenetic.
Shares Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome and the tag epigenetic.
Shares 4SC, Resminostat, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma).
Shares Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome and the tag epigenetic.
Shares 4SC, Resminostat.
Shares Belinostat, Romidepsin, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma).
Shares 4SC, Resminostat.
Shares Belinostat, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma).