在前列腺癌中,雄激素受体和DNA损伤反应途径之间的相互联系
Mallory Sands1, Samuel Adams1, Jihaeng Lee1
1Department of Biological Sciences, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN, USA.
Current urology
|October 8, 2025
概括
雄激素受体 (AR) 信号驱动前列腺癌,但抵抗性出现. 准AR和DNA损伤反应 (DDR) 途径为晚期前列腺癌治疗提供了新的希望.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
背景情况:
- 雄激素受体 (AR) 在前列腺癌的发展和进展中至关重要.
- 对AR向疗法的获得性耐药性是一个主要的临床障碍,通常与AR变化和同源重组缺陷 (HRD) 相关.
- HRD发生在大约20%的晚期前列腺癌病例中,导致基因组不稳定.
研究的目的:
- 审查AR在细胞过程中的作用.
- 探索AR和DNA损伤反应 (DDR) 途径之间的相互作用.
- 讨论前列腺癌治疗策略的最新进展,将AR向疗法与DDR向剂结合起来.
主要方法:
- 临床前和临床研究的文献综述.
- 分析AR信号和DDR通路之间的相互作用.
- 检查晚期前列腺癌的新兴治疗策略.
主要成果:
- AR活动影响DDR基因表达,DDR蛋白通常在AR调节区域附近发现.
- 像olaparib和rucaparib这样的多基聚合酶 (PARP) 抑制剂被FDA批准用于HRD阳性前列腺癌.
- 涉及AR向药物和DNA损伤或DNA修复抑制治疗的组合疗法正在研究中.
结论:
- AR和DDR路径之间的密切相互作用是一个有前途的治疗目标.
- 将AR向治疗与DNA损伤或修复抑制策略相结合,可以克服晚期前列腺癌的治疗耐药性.
- 对这些组合疗法的进一步研究是有必要的,以改善患者的治疗结果.
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