Until short time ago we considered cancer as the result of genetic mutations, but recent studies have shown that genetic mutations are not the only responsible for tumorigenesis. Although the genome contains all the information needed to encode the entire set of proteins, the expressio of this information is regulated by the epigenome. Hypermethylation is one of the best known epigenetic events in mammalian cells. Over the last few years, many studies have found that other epigenetic events, such as deacetylation and methylation of histones, are involved in the complex mechanism that regulates promoter transcription. Hypermethylation or histone deacethylation within the promoter of a tumor suppressor gene led to the silencing of that gene, as well as a deletion or a mutation. Pre-neoplastic lesions often show aberrant methylation and the frequency of aberrations increases with the progression of disease. Hypermethylation events can occur early in tumorigenesis, involving the disruption of pathways that may predispose cells to malignant transformation. The exact interplay of these factors in transcriptional repression activity is not yet well understood. Inhibitors of some of these are currently being studied as new drugs able to restore protein expression in cancer cells and to promote apoptosis and differentiation. Demethylating agents and histone deacetylase inhibitors are candidates for becoming potent new drugs in cancer therapy. This paper reviews current knowledge about epigenetic factors in the development of cancer and their role as new targets in anticancer therapy.
|Number of pages||14|
|Publication status||Published - Sep 2008|
- Anticancer drug combinations gene expression regulation
- DNA methylation inhibitors
- Histone deacethylase inhibitors
ASJC Scopus subject areas