Epigenetics in prostate cancer: Clinical implications

Abstract

Epigenetic alterations, including changes in DNA methylation, histone modifications and nucleosome remodeling, result in abnormal gene expression patterns that contribute to prostate tumor initiation and continue to evolve during the course of disease progression. Epigenetic modifications are responsible for silencing tumor-suppressor genes, activating oncogenic drivers, and driving therapy resistance and thus have emerged as promising targets for antineoplastic therapy in prostate cancer. In this review, we discuss the role of epigenetics in prostate cancer with a particular emphasis on clinical implications. We review how epigenetic regulators crosstalk with critical biological pathways, including androgen receptor signaling, and how these interactions dynamically control prostate cancer transcriptional profiles. Because of their potentially reversible nature, restoration of a "normal" epigenome could provide a basis for innovative therapeutic strategies in prostate cancer. We highlight how particular epigenetic alterations are emerging as potential diagnostic and prognostic biomarkers and/or targets for the treatment of advanced prostate cancer.