Hypomethylating Agents (HMAs) are a type of anticancer drugs that work by changing the expression of certain genes. To understand how these agents work, one has to know how our DNA works. The human DNA consists of a long stretch of DNA letters. Virtually all cells in the body share the exact same sequence of letters, referred to as the human genetic code or genome. While the genome is more than 99% identical for all humans, humans are far from identical. In fact, the differences between humans are the result of how the DNA is organized. In a sense, the organization of the DNA is similar to the organization of a text. While all texts are using the same 26 letters of the alphabet, it is the organization of these letters, the grammar and the punctuation that makes the alphabet useful and understandable. If a human genome is the sequence of letters, the “epigenome” is the punctuation. One important element of this epigenome consists of DNA methylation. In fact, by adding methyl groups to certain genes in the DNA, the expression of these genes can be altered.
Apart from changes to the DNA sequence (mutations), cancer cells also differ from healthy cells in the epigenomic organization of the genome. For example, cancer cells commonly display an excess or inappropriate DNA methylation. In fact, for several hematological malignancies, including myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), an abnormal DNA methylation is known to help the survival of cancer cells. To counter this cancerous process, HMAs have been developed that block the methylation of DNA through the inhibition of a protein called DNA methyltransferase. The most prominent of these agents, used for the treatment of patients with MDS, AML and other hematological malignancies consists of azacitidine.
HMAs are generally well tolerated drugs but, like all anticancer drugs, they can cause side effects The most common side effects of azacitidine consist of nausea and a skin rash on the injection site. In addition, some patients may also suffer from headaches, muscle pain and fever.
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