Towards targeted epigenetic therapy of cancer.
Increasing number of publications in the last 10 years implicated that cancer development depends, except genetic alterations, also on inheritable gene expression patterns that are not bound to DNA sequence alterations. These epigenetic mechanisms manifest mostly through changes in chromatin packing and in localized gene promoter changes that influence the transcription of the genes involved in carcinogenesis. These changes are mitoticaly inheritable and potentially reversible, providing large possibilities of epigenetic therapy of cancer. So far this therapy lacks specificity of targeting certain genes. Instead, epigenetic therapy attempts either to reactivate or to silence genes that are important for the cancer progress. Epigenetic therapy of cancer is based mostly on the usage of inhibitors of DNA methyltransferases (DNMTs), histone deacetylase (HDAC) inhibitors and anti-micro-RNA therapy. Developments that involve integration of the latest technological advances, such as whole genome microarray expression profiling, help identify mechanisms of action of epigenetic drugs, leading to development of second generation of epi-drugs which would have greater specificity and efficacy. The obtained results are promising, leaving great possibilities for improvement of cancer therapy.
Institute for Medical Research, Military Medical Academy, Belgrade, Serbia. zvonkomag@yahoo.co.uk
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D000107:Acetylation; D015254:DNA Modification Methylases / Q000235:genetics; D044127:Epigenesis, Genetic / Q000502:physiology*; D015316:Genetic Therapy / Q000379:methods*; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D035683:MicroRNAs / Q000235:genetics / Q000627:therapeutic use; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy*; D010597:Pharmacogenetics / Q000379:methods
D006657:Histones; D035683:MicroRNAs; D015254:DNA Modification Methylases