DNA and Histone Methylation in Prostate Cancer

As a model of “epigenetic catastrophe”, prostate cancer is driven by progressive epigenetic changes that arise early in carcinogenesis and persist throughout disease progression. In this chapter, two common epigenetic modifications, DNA methylation and histone methylation, are reviewed regarding their up-to-date roles in the disease. DNA hypermethylation at certain promoter regions is an early event during prostate tumorigenesis and epigenetically silences tumor suppressor genes. Genome-wide DNA hypomethylation is thought to activate oncogenes and becomes more extensive as the tumors become metastatic and aggressive. Dynamic regulation of histone methylation patterns leads to cancer-specific transcriptional profiles, and histone-modifying enzymes closely crosstalk with critical biological pathways such as the androgen receptor (AR) signaling. The functions and features of these two epigenetic programs make them highly promising as diagnostic and prognostic biomarkers or new therapeutic targets for prostate cancer. However, epigenetic therapy is still in its infancy and imposes a lot of challenging issues such as specificity, toxicity and potency. Therefore, we need to comprehensively understand the epigenetic regulatory mechanisms of prostate cancer development and progression, identify the pharmacodynamics and biomarkers of the epigenetic drugs targeting DNA methylation or histone methylation to better stratify patient populations who will likely benefit from the precision medicine.