Research prospects in the Cancer epigenome

Epigenetic mechanisms

Epigenome is equivalent to the word “genome”. It refers to the overall epigenetic state of a cell. Epigenetics is the study of heritable changes in gene expression or cellular phenotypes through processes other than the underlying DNA sequences.

Cancer epigenome could be the most important research topics in the coming time as its significance has been suggested in disease processes. Moreover, reversal of epigenetic abnormalities can be among the most important therapeutic strategies for cancer. Cancer researchers are also working on the epigenetic classifications in order to define more clearly the cancer subcategories.

Combination therapies are gaining potential but much research can be done in the combinations i.e. which combinations could work optimally against cancer? Furthermore, in certain combination therapies such as of Histone deacetylase (HDAC) inhibitor along with DNA methyltransferase inhibitors, final efficacy is still to be established.

Two of the recently approved drugs by U.S. Food and Drug Administration (FDA) are vorinostat (Zolinza; Merck) and romidepsin (Istodax; Celgene) as they are significantly efficient in cutaneous T-cell lymphoma but the precise molecular mechanisms for response in the patients have still to be cleared.

In cancer research, loss of gene functions, abnormal gains of DNA methylation in normally unmethylated gene promoter CpG Islands and associated stabilization of transcriptional repression are among highly studied epigenetic changes, which are thought to be the significant factors in earliest initiations in human cancer.

Role of DNA methylation from different prospects are emerging in the field of biology and most importantly in cancer research. Changes in methylation pattern in cancer cells have been found by the researchers but they are still unaware of the role of the changes. These changes are more frequent in cancer cells than in the nearby CpG islands and according to researchers these regional changes in cancer DNA methylation could be among the highly anticipated researches in the coming years. One of the recent proposals for mapping the patterns of DNA methylation is to identify the cancers of unknown primary site.

The mechanism through which vulnerable genes with promoter CpG islands undergo quantitative replacement of flexible, PcG-mediated gene silencing with the more stable silencing linked with DNA methylation is still to be fully elucidated.

Reference:

Stephen B. Baylin and Peter A. Jones, (2011). A decade of exploring the cancer epigenome — biological and translational implications. Nature Reviews Cancer, 11, 726-734. doi:10.1038/nrc3130

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