Epigenetic tools in potential anticancer therapy.
Human cancer represents a heterogeneous group of diseases that are driven by progressive genetic and epigenetic abnormalities. The latter alterations involve hypermethylation and hypomethylation of DNA, and changed patterns of histone modification, with resultant remodeling of the chromatin structure that cause deregulation of the transcription activity of many genes. Unlike the remarkable progress in understanding the processes by which DNA methyltransferases can regulate gene expression and histone deacetylases can induce alteration of chromatin structure, the roles of epigenetic events in tumors remain insufficiently explained. In contrast to genetic changes, the epigenetic alterations in cancer cells can be reversed by the inhibition of DNA methylation and histone deacetylation. Therefore, many inhibition agents for re-expression, predominantly of tumor-suppressor genes, have been identified and tested in laboratory models and numerous clinical trials. Despite in-vitro evidence that a single drug can lead to reactivation of methylated genes, inhibitors of DNA methyltransferases and histone deacetylases have been investigated in combination, or together with cytotoxic chemotherapy, radiotherapy, immunotherapy, or hormonal therapy to improve the therapeutic effect. Ongoing trials are recognizing that the identification of a target group of patients who are more likely to respond to the epigenetic therapy, defining of an optimal dose and schedule of treatment, and the development of more specific inhibitors with minimal unwanted side effects are necessary. Thus, new combinations of anticancer agents, including epigenetic modulators, may lead to a more effective control of cancer.
Sebova
Katarina
K
Laboratory of Cancer Genetics, Cancer Research Institute of Slovak Academy of Sciences, Bratislava, Slovakia.
Fridrichova
Ivana
I
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D044127:Epigenesis, Genetic; D015870:Gene Expression / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D015254:DNA Modification Methylases