前列腺癌中miRNA介导的抵抗机制:对向治疗和转移性进展的影响
Mostafa M Mostafa1, Mostafa K Abd El-Aziz2, Doha El-Sayed Ellakwa3,4
1Department of Molecular and Cellular Physiology, Stritch School of Medicine, Loyola University Chicago, Chicago, USA.
Medical oncology (Northwood, London, England)
|August 29, 2025
概括
本综述综合了微RNA (miRNA) 在前列腺癌治疗耐药性的作用,重点关注PI3K/AKT激活和EMT等机制. 它强调了基于miRNA的精确瘤学的挑战和未来方向.
科学领域:
- 癌症学
- 分子生物学
- 遗传学
背景情况:
- 前列腺癌 (PCa) 进展为抵抗割的疾病是由治疗阻力驱动的.
- 微RNAs (miRNAs) 参与PCa,但它们在抵抗途径中的特定作用需要集中合成.
- 现有的审查广泛涵盖了miRNA失调,需要以机制为中心的抗药途径.
研究的目的:
- 在标准PCa治疗 (ADT,恩扎胺,多塞塔克塞尔,放射治疗) 中合成miRNA介导的抗药机制.
- 专注于经过实验验证的miRNAs (例如,miR-21,miR-34a) 和它们在融合抵抗路径中的作用.
- 批判性地评估与治疗失败和适应性反应相关的miRNA失调的证据.
主要方法:
- 在PCa治疗耐药性中以机制为中心的miRNA功能的文献综述.
- 在PCa中强有力的实验验证的miRNA优先考虑.
- 对PI3K/AKT激活,EMT,DNA修复和AR变体信号传递等关键抗性机制中的miRNA作用的分析.
主要成果:
- 失调的miRNAs通过包括PI3K/ AKT激活,EMT和AR信号传递在内的机制促进PCa生存,干性和适应性反应.
- 细胞外囊泡 (EV) 介导的通信和缺氧驱动的信号传递被强调为关键的微环境因素.
- 循环的miRNA签名显示出作为生物标记物的潜力,但面临重大转化挑战.
结论:
- 目前在PCa疗法中的miRNA应用 (模仿剂,对抗剂) 是在研究中的,临床验证有限.
- 未来的进展需要在未来的试验和改进的交付平台 (例如基于电动汽车的系统) 中进行严格的验证.
- 将miRNA资料与临床和基因组数据相结合,对于推进PCa精确瘤学至关重要.
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