Environmental Carcinogenesis Lab, Food Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India.
Environmental Carcinogenesis Lab, Food Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India.
Vitam Horm. 2023;122:253-282. doi: 10.1016/bs.vh.2022.11.007. Epub 2022 Dec 29.
Prostate cancer (PCa) is one of the major health burdens among all cancer types in men globally. Early diagnosis and efficacious treatment options are highly warranted as far as the incidence of PCa is concerned. Androgen-dependent transcriptional activation of androgen receptor (AR) is central to the prostate tumorigenesis and therefore hormonal ablation therapy remains the first line of treatment for PCa in the clinics. However, the molecular signaling engaged in AR-dependent PCa initiation and progression is infrequent and diverse. Moreover, apart from the genomic changes, non-genomic changes such as epigenetic modifications have also been suggested as critical regulator of PCa development. Among the non-genomic mechanisms, various epigenetic changes such as histones modifications, chromatin methylation and noncoding RNAs regulations etc. play decisive role in the prostate tumorigenesis. Given that epigenetic modifications are reversible using pharmacological modifiers, various promising therapeutic approaches have been designed for the better management of PCa. In this chapter, we discuss the epigenetic control of tumor promoting AR signaling that underlies the mechanism of prostate tumorigenesis and progression. In addition, we have discussed the approaches and opportunities to develop novel epigenetic modifications based therapeutic strategies for targeting PCa including castrate resistant prostate cancer (CRPC).
前列腺癌(PCa)是全球男性所有癌症类型中主要的健康负担之一。就 PCa 的发病率而言,早期诊断和有效的治疗选择是非常必要的。雄激素依赖性转录激活雄激素受体(AR)是前列腺肿瘤发生的核心,因此激素消融疗法仍然是 PCa 临床治疗的一线方法。然而,参与 AR 依赖性 PCa 起始和进展的分子信号是罕见和多样化的。此外,除了基因组变化外,非基因组变化,如表观遗传修饰,也被认为是 PCa 发展的关键调节剂。在非基因组机制中,各种表观遗传变化,如组蛋白修饰、染色质甲基化和非编码 RNA 调节等,在前列腺肿瘤发生中起着决定性的作用。鉴于表观遗传修饰可以通过药理学修饰剂逆转,因此已经设计了各种有前途的治疗方法来更好地管理 PCa。在本章中,我们讨论了肿瘤促进 AR 信号的表观遗传控制,这是前列腺肿瘤发生和进展的机制。此外,我们还讨论了开发针对包括去势抵抗性前列腺癌(CRPC)在内的 PCa 的新型基于表观遗传修饰的治疗策略的方法和机会。