Abstract:
Prostate cancer is one of the most common malignancies among men worldwide. Besides genetic alterations, epigenetic modulations including DNA methylation, histone modifications and miRNA mediated alteration of gene expression are the key driving forces for the prostate tumor development and cancer progression. Aberrant expression and/or the activity of the epigenetic modifiers/enzymes, results in aberrant expression of genes involved in DNA repair, cell cycle regulation, cell adhesion, apoptosis, autophagy, tumor suppression and hormone response and thereby disease progression. Altered epigenome is associated with prostate cancer recurrence, progression, aggressiveness and transition from androgen-dependent to androgen-independent phenotype. These epigenetic modifications are reversible and various compounds/drugs targeting the epigenetic enzymes have been developed that are effective in cancer treatment. This chapter focuses on the epigenetic alterations in prostate cancer initiation and progression, listing different epigenetic biomarkers for diagnosis and prognosis of the disease and their potential as therapeutic targets. This chapter also summarizes different epigenetic drugs approved for prostate cancer therapy and the drugs available for clinical trials.
摘要:
前列腺癌是全世界男性中最常见的恶性肿瘤之一。除了遗传改变,表观遗传调制,包括DNA甲基化,组蛋白修饰和miRNA介导的基因表达改变是前列腺肿瘤发生和进展的关键驱动力。表观遗传修饰剂/酶的异常表达和/或活性,导致参与DNA修复的基因表达异常,细胞周期调节,细胞粘附,凋亡,自噬,肿瘤抑制和激素反应,从而疾病进展。表观基因组改变与前列腺癌复发有关,programming,侵袭性和从雄激素依赖性到雄激素非依赖性表型的转变。这些表观遗传修饰是可逆的,并且已经开发了在癌症治疗中有效的靶向表观遗传酶的各种化合物/药物。本章重点介绍前列腺癌发生和进展的表观遗传学改变,列出了用于疾病诊断和预后的不同表观遗传生物标志物及其作为治疗靶标的潜力。本章还总结了批准用于前列腺癌治疗的不同表观遗传药物以及可用于临床试验的药物。