{"entity":{"id":"hdac","kind":"target","name":"Histone deacetylases (HDAC)","aka":[],"tldr":"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.","summary":"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in cutaneous T-cell lymphoma, belinostat and romidepsin in peripheral T-cell lymphoma, and panobinostat (US approval withdrawn) in multiple myeloma.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.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Histone_deacetylase","links":[{"label":"NCBI Gene HDAC1","url":"https://www.ncbi.nlm.nih.gov/gene/3065"}],"tags":["epigenetic"],"related":[],"cancers":["peripheral-t-cell-lymphoma","multiple-myeloma"],"sections":[],"technologies":[],"targets":[],"drugs":["romidepsin","belinostat","vorinostat","abt-301"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Prevalence not recorded as a positivity rate: HDACs are expressed in essentially all cells and HDAC inhibitors are not selected on target expression. Published series report continuous or cutoff-dependent expression rather than a positivity rate: Mithraprabhu 2014 found HDAC1 protein detectable in most myeloma trephines and compared >=90% with <=20% cell positivity for prognosis (doi:10.4161/15592294.2014.983367); Min 2012 graded HDAC1-3 expression in 13 PTCL-NOS and 78 DLBCL (doi:10.4132/KoreanJPathol.2012.46.2.142)."],"symbol":"HDAC1, HDAC2, HDAC3, HDAC6","role":[],"sources":[],"specificity":"broadly-expressed","distribution":"few-types","specificityNote":"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.)","specificitySources":[{"label":"Human Protein Atlas HDAC1 tissue","url":"https://www.proteinatlas.org/ENSG00000116478-HDAC1/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas HDAC2 tissue","url":"https://www.proteinatlas.org/ENSG00000196591-HDAC2/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas HDAC3 tissue","url":"https://www.proteinatlas.org/ENSG00000171720-HDAC3/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Human Protein Atlas HDAC6 tissue","url":"https://www.proteinatlas.org/ENSG00000094631-HDAC6/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000116478 associations","url":"https://platform.opentargets.org/target/ENSG00000116478/associations","note":"cancer associations at or above 0.5 (CC0)"},{"label":"Open Targets ENSG00000196591 associations","url":"https://platform.opentargets.org/target/ENSG00000196591/associations","note":"cancer associations at or above 0.5 (CC0)"}],"biology":"Inhibition causes histone hyperacetylation, cell-cycle arrest via p21 induction, apoptosis and reduced angiogenesis; class-related toxicities are fatigue, thrombocytopenia, diarrhoea and QT prolongation.","whereFound":["Cutaneous T-cell lymphoma","Peripheral T-cell lymphoma","Multiple myeloma (panobinostat)"],"targetClass":"enzyme","prevalence":[]},"route":"/targets/hdac/","neighbours":{"cancer":[{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"}],"drug":[{"id":"abt-301","kind":"drug","name":"ABT-301","route":"/drugs/abt-301/"},{"id":"belinostat","kind":"drug","name":"Belinostat","route":"/drugs/belinostat/"},{"id":"resminostat","kind":"drug","name":"Resminostat","route":"/drugs/resminostat/"},{"id":"romidepsin","kind":"drug","name":"Romidepsin","route":"/drugs/romidepsin/"},{"id":"vorinostat","kind":"drug","name":"Vorinostat","route":"/drugs/vorinostat/"}],"roadmap":[{"id":"epigenetics-roadmap","kind":"roadmap","name":"Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome","route":"/roadmaps/epigenetics-roadmap/"}],"company":[{"id":"4sc","kind":"company","name":"4SC","route":"/companies/4sc/"}]}}