ire1 α-介导的UPR在胃肠道肿瘤中的激活：适应机制和治疗潜力。

IF 7.5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Drug Discovery Today Pub Date : 2025-04-01 DOI:10.1016/j.drudis.2025.104335

Valappan Veetil Soumya , Baby Jisna , Davis Anu , Chevookaren Francis Binoy , Thekkekara Devassy Babu

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引用次数: 0

摘要

内质网在蛋白质合成、折叠和质量控制中起着至关重要的作用。这些过程的中断导致内质网应激（ERS）并激活未折叠蛋白反应（UPR）以恢复细胞稳态。在胃肠道癌症中，肌醇要求酶1α (IRE1α)是UPR的关键调节因子，帮助癌细胞适应缺氧、氧化应激和化疗等不利条件。升高的IRE1α活性通过减轻ers诱导的细胞凋亡来支持肿瘤存活、进展和转移。然而，靶向IRE1α信号是一种很有前景的治疗策略，可能会损害癌细胞对应激的适应并提高治疗效果。靶向IRE1α为胃肠道癌症提供了有希望的治疗机会。

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IRE1α-mediated UPR activation in gastrointestinal cancers: Adaptive mechanisms and therapeutic potential

The endoplasmic reticulum (ER) plays a crucial role in protein synthesis, folding and quality control. Disruptions in these processes lead to ER stress (ERS) and activate the unfolded protein response (UPR) to restore cellular homeostasis. In gastrointestinal cancers, inositol-requiring enzyme 1α (IRE1α) is a key regulator of the UPR, enabling cancer cells to adapt to hostile conditions such as hypoxia, oxidative stress and chemotherapy. Elevated IRE1α activity supports tumor survival, progression and metastasis by mitigating ERS-induced apoptosis. However, targeting IRE1α signaling presents a promising therapeutic strategy by impairing cancer cell adaptation to stress, offering promising therapeutic opportunities for gastrointestinal cancers.

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来源期刊

Drug Discovery Today 医学-药学

CiteScore

14.80

自引率

2.70%

发文量

293

审稿时长

6 months

期刊介绍： Drug Discovery Today delivers informed and highly current reviews for the discovery community. The magazine addresses not only the rapid scientific developments in drug discovery associated technologies but also the management, commercial and regulatory issues that increasingly play a part in how R&D is planned, structured and executed. Features include comment by international experts, news and analysis of important developments, reviews of key scientific and strategic issues, overviews of recent progress in specific therapeutic areas and conference reports.