Claes B, Buysschaert I, Lambrechts D. Pharmaco-epigenomics: discovering therapeutic approaches and biomarkers for cancer therapy. Heredity 2010 Jul;105(1):152-160. (Review)
doi:10.1038/hdy.2010.42
http://www.nature.com/hdy/journal/v105/n1/abs/hdy201042a.html
http://www.nature.com/hdy/journal/v105/n1/full/hdy201042a.html
http://www.nature.com/hdy/journal/v105/n1/pdf/hdy201042a.pdf
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Review
Heredity (2010) 105, 152–160; doi:10.1038/hdy.2010.42; published online 14 April 2010
Pharmaco-epigenomics: discovering therapeutic approaches and biomarkers for cancer therapy
B Claes1, I Buysschaert1 and D Lambrechts1
1Vesalius Research Center, VIB and K.U.Leuven, Campus Gasthuisberg, Leuven, Belgium
Correspondence: Professor D Lambrechts, Vesalius Research Center, VIB and K.U.Leuven Campus Gasthuisberg, Herestraat 49, box 912, B-3000, Leuven, Belgium. E-mail: diether.lambrechts@vib-kuleuven.be
Received 26 November 2009; Revised 24 February 2010; Accepted 25 February 2010; Published online 14 April 2010.
Abstract
An important feature of cancer is dysregulation of gene activity and gene expression, which is driven by a combination of acquired genetic and epigenetic alterations. Here, we will highlight how insights into the epigenetic processes underpinning tumor biology have led to the emerging field of cancer pharmaco-epigenomics. First, we will discuss how interference with the epigenetic machinery in cancer is leading to novel promising therapies, with several DNA methyltransferase and histone deacetylase inhibitors being approved for cancer treatment. Second, we will discuss how epigenetic markers in cancer may increasingly be used as complementary diagnostic tools, prognostic markers of disease progression, and predictive markers of treatment response. Although the anti-tumoral activities of epigenetic therapies have thus far been attributed to reactivation of silenced tumor-suppressor and/or apoptotic genes, they may also influence the tumor environment by directly affecting stromal cells. As an example, we will discuss how tumor-endothelial cells are regulated at the epigenetic level and are affected by methyltransferase and histone deacetylase inhibitors.
Keywords: pharmaco-epigenomics; DNA methylation; histone modification; cancer therapy; angiogenesis; biomarker