Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People's Republic of China.
Department of Biobank, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People's Republic of China.
Cell Commun Signal. 2022 Nov 7;20(1):174. doi: 10.1186/s12964-022-00964-7.
Recurrence, metastasis, and drug resistance are still big challenges in breast cancer therapy. Internal and external stresses have been proven to substantially facilitate breast cancer progression through molecular and systemic mechanisms. For example, endoplasmic reticulum stress (ERS) results in activation of the unfolded protein response (UPR), which are considered an important cellular stress response. More and more reports indicate its key role in protein homeostasis and other diverse functions involved in the process of breast cancer progression. Therefore, therapies targeting the activation of ERS and its downstream signaling pathways are potentially helpful and novel tools to counteract and fight breast cancer. However, recent advances in our understanding of ERS are focused on characterizing and modulating ERS between healthy and disease states, and so little attention has been paid to studying the role and clinical application of targeting ERS in a certain cancer. In this review, we summarize the function and main mechanisms of ERS in different molecular types of breast cancer, and focus on the development of agents targeting ERS to provide new treatment strategies for breast cancer. Video Abstract.
复发、转移和耐药仍然是乳腺癌治疗的重大挑战。内外应激已被证明通过分子和系统机制极大地促进了乳腺癌的进展。例如,内质网应激(ERS)导致未折叠蛋白反应(UPR)的激活,这被认为是一种重要的细胞应激反应。越来越多的报告表明其在蛋白质动态平衡和其他与乳腺癌进展过程相关的多种功能中的关键作用。因此,靶向 ERS 激活及其下游信号通路的治疗方法可能是对抗和治疗乳腺癌的有帮助和新颖的工具。然而,目前我们对 ERS 的理解进展主要集中在描述和调节健康和疾病状态之间的 ERS,因此很少关注研究靶向 ERS 在特定癌症中的作用和临床应用。在这篇综述中,我们总结了 ERS 在不同分子类型乳腺癌中的功能和主要机制,并重点介绍了靶向 ERS 的药物的开发,为乳腺癌提供新的治疗策略。视频摘要。