Maekawa Shigekatsu, Takata Ryo, Obara Wataru
Department of Urology, Iwate Medical University, Iwate 028-3694, Japan.
Cancers (Basel). 2024 Jan 25;16(3):523. doi: 10.3390/cancers16030523.
The progression of prostate cancer (PCa) relies on the activation of the androgen receptor (AR) by androgens. Despite efforts to block this pathway through androgen deprivation therapy, resistance can occur through several mechanisms, including the abnormal activation of AR, resulting in castration-resistant PCa following the introduction of treatment. Mutations, amplifications, and splicing variants in AR-related genes have garnered attention in this regard. Furthermore, recent large-scale next-generation sequencing analysis has revealed the critical roles of AR and AR-related genes, as well as the DNA repair, PI3K, and cell cycle pathways, in the onset and progression of PCa. Moreover, research on epigenomics and microRNA has increasingly become popular; however, it has not translated into the development of effective therapeutic strategies. Additionally, treatments targeting homologous recombination repair mutations and the PI3K/Akt pathway have been developed and are increasingly accessible, and multiple clinical trials have investigated the efficacy of immune checkpoint inhibitors. In this comprehensive review, we outline the status of PCa research in genomics and briefly explore potential future developments in the field of epigenetic modifications and microRNAs.
前列腺癌（PCa）的进展依赖于雄激素对雄激素受体（AR）的激活。尽管通过雄激素剥夺疗法努力阻断这一途径，但仍可通过多种机制产生耐药性，包括AR的异常激活，导致治疗后出现去势抵抗性PCa。AR相关基因的突变、扩增和剪接变体在这方面已受到关注。此外，最近的大规模下一代测序分析揭示了AR和AR相关基因以及DNA修复、PI3K和细胞周期途径在PCa发生和进展中的关键作用。此外，表观基因组学和微小RNA的研究越来越受欢迎；然而，它尚未转化为有效的治疗策略。此外，针对同源重组修复突变和PI3K/Akt途径的治疗方法已经开发出来且越来越容易获得，并且多项临床试验已经研究了免疫检查点抑制剂的疗效。在这篇综述中，我们概述了PCa基因组学研究的现状，并简要探讨了表观遗传修饰和微小RNA领域未来潜在的发展。
