Epigenetic Therapies of Cancer
Abstract:Modification of chromatin without actually altering its nucleotide sequence is termed epigenetic modification. These modifications include changes in methylation, acetylation and phosphorylation levels of histones as well as methylation of CpG islands in DNA. Besides these covalent modifications, ATP-dependent alterations of chromatin topology also represent another level of chromatin remodeling. All these changes eventually affect expression of various proteins. Condensation of chromatin structure to a heterochromatin form leads to silencing of genes whereas decondensation to euchromatin structures is associated with de-repression. In general, acetylation of lysine residues in histones leads to increased expression while methylation of these residues results in silencing. Methylation of CpG islands can also lead to gene silencing.
Since cancer is associated with aberrant expression of various genes caused by epigenetic alteration that are essentially reversible, targeting epigenetic modifications may serve as a useful tool to design strategies for cancer therapy. In the past few years, serious efforts were bestowed to explore this possibility and different pathways are being tested for their usefulness as anti-cancer targets. These targets include the cell cycle, apoptosis and angiogenesis regulatory genes. Another interesting epigenetic approach under investigation is to induce senescence in tumor cells. This is based on the theory that senescence is a potential tumor suppressor mechanism.
In this review we summarize recent findings aimed towards exploiting epigenetic modification as potent cancer therapeutic strategies with special emphasis on cell cycle, senescence, apoptosis and angiogenesis related genes.
Document Type: Research Article
Affiliations: Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, M320, Houston, TX 77030, USA.
Publication date: May 1, 2006
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