Department of Pathology, Duke University School of Medicine, Durham, NC, 27710, USA.
Duke Cancer Institute, Duke University School of Medicine, Durham, NC, 27710, USA.
Cancer Treat Res. 2023;190:321-360. doi: 10.1007/978-3-031-45654-1_10.
Prostate cancer (PCa) is a heterogeneous disease exhibiting both genetic and epigenetic deregulations. Epigenetic alterations are defined as changes not based on DNA sequence, which include those of DNA methylation, histone modification, and chromatin remodeling. Androgen receptor (AR) is the main driver for PCa and androgen deprivation therapy (ADT) remains a backbone treatment for patients with PCa; however, ADT resistance almost inevitably occurs and advanced diseases develop termed castration-resistant PCa (CRPC), due to both genetic and epigenetic changes. Due to the reversible nature of epigenetic modifications, inhibitors targeting epigenetic factors have become promising anti-cancer agents. In this chapter, we focus on recent studies about the dysregulation of epigenetic regulators crucially involved in the initiation, development, and progression of PCa and discuss the potential use of inhibitors targeting epigenetic modifiers for treatment of advanced PCa.
前列腺癌 (PCa) 是一种具有遗传和表观遗传失调的异质性疾病。表观遗传改变是指不基于 DNA 序列的变化,包括 DNA 甲基化、组蛋白修饰和染色质重塑。雄激素受体 (AR) 是 PCa 的主要驱动因素,去势治疗 (ADT) 仍然是 PCa 患者的主要治疗方法;然而,由于遗传和表观遗传的改变,ADT 几乎不可避免地会产生耐药性,导致晚期疾病发展为去势抵抗性前列腺癌 (CRPC)。由于表观遗传修饰的可逆性,靶向表观遗传因子的抑制剂已成为有前途的抗癌药物。在这一章中,我们重点介绍了最近关于表观遗传调控因子失调的研究,这些调控因子在 PCa 的发生、发展和进展中起着关键作用,并讨论了靶向表观遗传修饰剂抑制剂用于治疗晚期 PCa 的潜在用途。