Histone deacetylases (HDAC)
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.
Overview
Histone deacetylases remove acetyl groups from lysines on histones and many non-histone proteins (p53, HSP90, 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in cutaneous T-cell lymphoma, belinostat and romidepsin in peripheral T-cell lymphoma, and panobinostat (US approval withdrawn) in multiple myeloma.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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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 · How drugs use it
1 product aims at Histone deacetylases (HDAC): small molecules. Inhibitors are shaped to fit the enzyme's active site so the reaction the cancer relies on stops.
Elsewhere
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.
- Cutaneous T-cell lymphoma
- Peripheral T-cell lymphoma
- Multiple myeloma (panobinostat)
Latest papers
topQuery 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.