Epigenetic Alterations in Bladder Cancer and Their Potential Clinical Implications

Figure 2

Epigenetic therapies can reverse aberrant epigenetic modifications in cancer. Genes that are expressed in normal cells, such as tumor suppressor genes, have an open chromatin structure, consisting of an unmethylated promoter, active histone marks, and a nucleosome-free region immediately upstream of the transcription start site. During tumorigenesis, genes can be silenced through one of the two silencing mechanisms: polycomb repressive complex (PRC) reprogramming and de novo DNA methylation. PRC-mediated silencing can be reversed upon treatment with EZH2 inhibitors, such as DZnep. The de novo methylation-mediated silencing can be reversed upon treatment with DNA methylation transferase inhibitors, such as 5-Aza-CdR, 5-Aza-CR, Zebularine, and S110. The therapeutic value of above reagents may be enhanced when combining with HDAC inhibitors, such as SAHA, PBA, and TSA. Open and closed circles represent unmethylated and methylated CpG sites, respectively.