内质网 (ER) 是协调蛋白质折叠和脂质生物合成等关键细胞功能的重要细胞器。然而，它对导致内质网应激的干扰高度敏感。作为回应，未折叠蛋白反应 (UPR) 激活以恢复内质网稳态，主要通过三个传感器：IRE1、ATF6 和 PERK。 ERAD 和自噬对于缓解 ER 应激至关重要，但它们的失调可能导致错误折叠蛋白的积累。顺铂是一种常用的化疗药物，可诱导肿瘤细胞内质网应激，激活复杂的信号通路。对顺铂的耐药性源于药物积累减少、DNA 修复激活和抗凋亡机制。值得注意的是，顺铂诱导的内质网应激可以双重影响肿瘤细胞，根据具体情况促进肿瘤细胞存活或凋亡。 ERAD 对于降解错误折叠蛋白至关重要，而自噬可以保护细胞免于凋亡或增强 ER 应激诱导的细胞凋亡。 ER 应激、顺铂耐药、ERAD 和自噬之间复杂的相互作用为癌症治疗开辟了新途径。了解这些过程可能会导致克服化疗耐药性的创新策略，从而有可能改善基于顺铂的癌症治疗的结果。这篇综合综述对 ER 应激、顺铂耐药的复杂机制及其在癌症治疗中的影响提供了多方面的视角。版权所有 © 2024 Mu、Zhi、Zhou、Wang、Chai、Fan 和 Lv。

The endoplasmic reticulum (ER) is a crucial organelle that orchestrates key cellular functions like protein folding and lipid biosynthesis. However, it is highly sensitive to disturbances that lead to ER stress. In response, the unfolded protein response (UPR) activates to restore ER homeostasis, primarily through three sensors: IRE1, ATF6, and PERK. ERAD and autophagy are crucial in mitigating ER stress, yet their dysregulation can lead to the accumulation of misfolded proteins. Cisplatin, a commonly used chemotherapy drug, induces ER stress in tumor cells, activating complex signaling pathways. Resistance to cisplatin stems from reduced drug accumulation, activation of DNA repair, and anti-apoptotic mechanisms. Notably, cisplatin-induced ER stress can dualistically affect tumor cells, promoting either survival or apoptosis, depending on the context. ERAD is crucial for degrading misfolded proteins, whereas autophagy can protect cells from apoptosis or enhance ER stress-induced apoptosis. The complex interaction between ER stress, cisplatin resistance, ERAD, and autophagy opens new avenues for cancer treatment. Understanding these processes could lead to innovative strategies that overcome chemoresistance, potentially improving outcomes of cisplatin-based cancer treatments. This comprehensive review provides a multifaceted perspective on the complex mechanisms of ER stress, cisplatin resistance, and their implications in cancer therapy.Copyright © 2024 Mu, Zhi, Zhou, Wang, Chai, Fan and Lv.