内质网膜应激在抗癌药物耐药性中的隐藏作用
Joyeeta T Khan1, Saloni Sood1, Veronica Piedra2
1Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
细胞内膜网膜应激 (ERS) 和未展开的蛋白质反应 (UPR) 帮助癌细胞存活和抵抗药物. 准UPR通路可能会使瘤对治疗更敏感.
科学领域:
- 细胞生物学 细胞生物学
- 在瘤学瘤学.
- 分子医学是分子医学.
背景情况:
- 细胞内膜网膜应激 (ERS) 和未折叠的蛋白质反应 (UPR) 对癌细胞存活和耐药性至关重要.
- UPR的激活涉及PERK,IRE1α和ATF6通路,促进瘤细胞的适应.
- 这些适应机制有助于癌症转移和对治疗的抗性.
研究的目的:
- 审查ERS-UPR信号如何在各种癌症中促进瘤弹性.
- 评估针对癌症治疗的UPR途径的治疗潜力.
主要方法:
- 对癌症中的ERS-UPR信号研究的文献综述.
- 对UPR激活的基础分子机制及其在瘤适应中的作用的分析.
- 针对UPR组件的治疗策略的评估.
主要成果:
- ERS-UPR信号增强了癌细胞的生存,转移和治疗耐药性.
- 像PERK-eIF2α-ATF4,IRE1α-XBP1和ATF6这样的特定途径促进了瘤的弹性.
- 用像GSK2606414或MKC-3946这样的抑制剂准UPR显示了治疗潜力.
结论:
- ERS-UPR信号传输是乳腺癌,前列腺癌,结直肠癌和胰腺癌中瘤弹性的关键驱动力.
- 调节UPR提供了一个有希望的策略,使瘤对传统和向治疗重新敏感.
- 针对UPR提出了一种双重的治疗方法:抑制或加剧ER压力.
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