Unlike mutations, epigenetic changes can be reversed. This makes them targets for drugs. The aim of epigenetic treatment is to reactivate tumour suppressor genes that have been wrongly silenced, so they can slow cell division again or trigger apoptosis in cancer cells.Drugs that reduce DNA methylation
Hypermethylation silences tumour suppressor genes. Drugs such as azacitidine and decitabine inhibit the enzymes that add methyl groups to DNA (DNA methyltransferases). When the cancer cells divide, the new DNA is not methylated, so the tumour suppressor genes can be transcribed again. These drugs are used to treat some blood cancers.Drugs that increase histone acetylation
Deacetylation of histones condenses chromatin and silences genes. HDAC inhibitors block histone deacetylase enzymes, so the histones stay acetylated, the chromatin stays less condensed, and tumour suppressor genes can be transcribed.Evaluating these treatments
• They are not specific: the enzymes they inhibit act in healthy cells too, so other genes, including proto-oncogenes, may be wrongly switched on, causing side effects.
• Methylation inhibitors act mainly on dividing cells, such as cancer cells, but other rapidly dividing cells, such as those in bone marrow, are affected too.
• They cannot correct cancers caused only by mutations, because they do not change the base sequence.Worked example: in a trial, 120 patients received a methylation inhibitor and 48 went into remission.percentage remission = 48 ÷ 120 × 100 = 40% To judge the drug, this must be compared with a control group given the standard treatment.
Hypermethylation silences tumour suppressor genes. Drugs such as azacitidine and decitabine inhibit the enzymes that add methyl groups to DNA (DNA methyltransferases). When the cancer cells divide, the new DNA is not methylated, so the tumour suppressor genes can be transcribed again. These drugs are used to treat some blood cancers.Drugs that increase histone acetylation
Deacetylation of histones condenses chromatin and silences genes. HDAC inhibitors block histone deacetylase enzymes, so the histones stay acetylated, the chromatin stays less condensed, and tumour suppressor genes can be transcribed.Evaluating these treatments
• They are not specific: the enzymes they inhibit act in healthy cells too, so other genes, including proto-oncogenes, may be wrongly switched on, causing side effects.
• Methylation inhibitors act mainly on dividing cells, such as cancer cells, but other rapidly dividing cells, such as those in bone marrow, are affected too.
• They cannot correct cancers caused only by mutations, because they do not change the base sequence.Worked example: in a trial, 120 patients received a methylation inhibitor and 48 went into remission.