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Epigenetic Therapy

  • Date Submitted: 08/07/2010 04:16 AM
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Epigenetic Therapy
A New Approach To Treat Cancer

Epigenetic mechanisms in normal cells:
Chromatin is made of repeating units of nucleosomes, which   consist of 146 base pairs of DNA wrapped around an octamer of four core histone proteins (H3, H4, H2A and H2B). Epigenetic mechanisms that modify chromatin structure can be divided into four main categories: DNA methylation, covalent histone modifications, non-covalent mechanisms such as incorporation of histone variants and nucleosome remodeling and non-coding RNAs including microRNAs (miRNAs). These modifications work together to regulate the functioning of the genome by altering the local structural dynamics of chromatin, primarily regulating its accessibility and compactness. The interplay of these modifications creates an ‘epigenetic landscape’ that regulates the way the mammalian genome manifests itself in different cell types, developmental stages and disease states, including cancer. The distinct patterns of these modifications present in different cellular states serve as a guardian of cellular identity. Here, we will discuss the important aspects of the key epigenetic mechanisms present in normal cells.

Aberrant reprogramming of the epigenome in cancer:
The precise epigenomic landscape present in normal cells undergoes extensive distortion in cancer. These epimutations, along with widespread genetic alterations, play an important role in cancer initiation and progression. The cancer epigenome is characterized by global changes in DNA methylation and histone modification patterns as well as altered expression profiles of chromatin-modifying enzymes. These epigenetic changes result in global dysregulation of gene expression profiles leading to the development and progression of disease states. Epimutations can lead to silencing of tumor suppressor genes independently and also in conjunction with deleterious genetic mutations or deletions; thus, serving as the second hit required for cancer initiation...


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