Epigenetic approaches to prostate cancer: Present landscape and future prospects

Abstract

Genetic profiles alone do not fully describe the development and evolution of prostate cancer (PCa), whereas epigenetic alterations are emerging as promising therapeutic targets. This review explores FDA-approved and experimental epigenetic strategies, including DNA methyltransferase inhibitors (DNMTis), histone deacetylase inhibitors (HDACis), histone methyltransferase inhibitors, bromodomain and extra-terminal domain inhibitors (BETi), non-coding RNA therapies, antisense oligonucleotides, and future prospects such as chromatin remodeling, DNA hydroxymethylation, and RNA methylation. Although DNMTis and HDACis have historically dominated clinical trials, mainly in hematologic cancers, the 2020 approval of an epigenetic therapy for a solid tumor marked an important breakthrough. Despite this, epigenetic drugs remain underexplored in PCa: among 2254 clinical studies of such agents, only 58 (2.57 %) included PCa patients. This disparity highlights an urgent need for novel therapeutic approaches beyond chemotherapy and androgen deprivation. By assessing current progress and outlining opportunities in drug repositioning and novel targets, this review underscores epigenetics as a critical frontier for advancing PCa treatment.