HDAC inhibitor
Meaning of HDAC inhibitor: The short form used in oncology for drugs acting on the packaging of DNA rather than on the sequence written in it.
Definition of HDAC inhibitor
HDAC inhibitor is the abbreviation for histone deacetylase inhibitor, a class of drug that acts on how tightly DNA is wound rather than on the genetic code itself. Blocking histone deacetylase enzymes keeps acetyl tags attached to the histone spools, loosening the coil so that silenced genes can be read once more. Several are approved for uncommon lymphomas.
What does epigenetic mean here?
An epigenetic change alters which genes a cell uses without altering a single letter of its DNA. Every cell in the body carries the same code; what makes a liver cell differ from a nerve cell is which portions are open for reading and which are packed away. Tags on the histone deacetylase substrate and on the DNA itself are what set that pattern, and it is copied when a cell divides. A tumor can silence a protective gene by packing it away, leaving the gene intact but unusable, and that is the state these drugs aim to reverse.
How do the epigenetic drugs compare?
| Class | What it acts on | Examples |
|---|---|---|
| HDAC inhibitors | Acetyl tags on histones | Vorinostat, romidepsin, belinostat |
| DNA methyltransferase inhibitors | Methyl tags on DNA | Azacitidine, decitabine |
| EZH2 inhibitors | A specific histone methyl mark | Tazemetostat |
Why do tumor cells suffer more than normal ones?
The honest answer is that it is not fully understood. Two explanations are offered. Tumor cells often depend on having silenced particular protective genes, so reopening them removes something the tumor was relying on. They also run at a higher level of internal stress, with more misfolded protein and more DNA damage already present, and cope less well with a further disturbance. Blood cancers respond far better than solid tumors, and the reason for that difference is also unsettled.
Where do they sit among cancer drugs?
They are grouped with targeted agents because each binds a defined enzyme, but their consequences are wide, since gene activity shifts across the cell. Panobinostat has been combined with a proteasome inhibitor in myeloma, the reasoning being that both interfere with how a cell handles unwanted protein. Fatigue, gut upset, low platelets and effects on heart rhythm are the recognized problems of the class. Some agents block many of the enzyme family at once, while newer ones aim at a narrower subset. Full detail sits under histone deacetylase inhibitor.
Also known as
Used in a sentence
An HDAC inhibitor was included in the regimen after earlier lines of treatment failed.
Good to know
These drugs change which genes a cell can read without altering the genetic code, and several are licensed treatments rather than investigational compounds.