在实验性抗癌疗法中对内质网膜应激的调节
1Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 Thorez Avenue, Saint-Petersburg 194223, Russia.
International journal of molecular sciences
|July 12, 2025
概括
准细胞内膜网膜应激 (ERS) 和未展开的蛋白质反应 (UPR) 为增强癌症化疗提供了一种新的策略. 诱导ERS或抑制UPR的化合物显示出临床前前景,但需要进一步开发用于临床使用.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 瘤生长涉及增加的内等质网膜应激 (ERS) 和展开的蛋白质反应 (UPR) 激活.
- 通常情况下,UPR会恢复ER蛋白质稳定,但长时间的ERS会诱导细胞死亡,从而呈现出治疗的脆弱性.
- 在各种癌症中,ERS/UPR机械组件的调节失调,建议将其作为战略目标.
研究的目的:
- 审查针对癌症治疗的ERS/UPR途径的天然和合成化合物.
- 探索涉及过度ESR诱导或抑制UPR的治疗策略.
- 讨论ERS/UPR抑制剂的分子机制和临床潜力.
主要方法:
- 关于ERS/UPR调节剂的文献叙述审查.
- 针对ER Ca2+ (SERCA) 和UPR传感器 (GRP78,PERK,IRE1α,ATF6) 的化合物的分析.
- 检查由ERS/UPR抑制剂诱导的分子变化.
主要成果:
- 几种药物表现出有希望的临床前组合疗法效果.
- 抑制剂可以破坏ER Ca2+稳态或损害蛋白质降解信号.
- 临床试验数据有限且不一致,具有显著的副作用和生物可用性问题.
结论:
- 药理学调节ERS/UPR是一种可行的方法,可以使癌细胞对化疗敏感.
- 开发更有选择性,更稳定,更少毒性的药物至关重要.
- 需要改进的输送系统来增强治疗特异性和临床应用.
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