A hypomethylating agent (or demethylating agent
) is a drug that inhibits
DNA methylation
DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts t ...
: the modification of DNA nucleotides by addition of a methyl group. Because DNA methylation affects cellular function through successive generations of cells without changing the underlying DNA sequence, treatment with a hypomethylating agent is considered a type of
epigenetic therapy
Epigenetic therapy is the use of drugs or other epigenome-influencing techniques to treat medical conditions. Many diseases, including cancer, heart disease, diabetes, and mental illnesses are influenced by epigenetic mechanisms. Epigenetic th ...
.
Currently available hypomethylating agents block the activity of
DNA methyltransferase (DNA methyltransferase inhibitors / DNMT inhibitors).
Currently two members of the class,
azacitidine and
decitabine, are FDA-approved for use in the United States in
myelodysplastic syndrome and are being investigated for use in a number of
tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
s.
Clinical use
Two hypomethylating agents are approved for the treatment of
myelodysplastic syndrome by the United States FDA
*
decitabine Also has EU approval for
acute myeloid leukemia (AML).
*
azacitidine
Mechanism of action
DNA methylation is the modification of DNA nucleotides by addition of a methyl group. These methyl groups are associated with changes in the ability of the corresponding DNA to be used. Patterns of DNA methylation are stable during cellular division. Methylation of
tumor suppressor
A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or red ...
genes in some cancers contributes to the growth and survival of the cancer. Hypomethylating agents decrease the amount of cellular DNA methylation, allowing for tumor suppressor gene expression.
See also
*
DNA methyltransferase
References
Antineoplastic drugs
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