未折叠蛋白应激（UPR）是一种细胞机制，在内质网（ER）中蛋白质错误折叠积累的应激条件下保护细胞。UPR激活三条信号通路，以缓解应激条件，促进细胞稳态和细胞存活。然而，在无法缓解的应激条件下，UPR激活信号转变为通过凋亡促进细胞死亡。有趣的是，癌细胞利用这条通路在长时间应激条件下促进细胞存活并避免凋亡。在这里，我们讨论与UPR相关的不同信号通路，并专注于UPR激活时的一条ER信号转导通路：肌醇需要酶1α（IRE1）。我们的理由是IRE1通路与细胞命运决策有关，并被认为是癌症治疗的有希望的靶点。在这里，我们讨论IRE1抑制剂以及它们可能成为有效的癌症治疗方法。© 2023. 作者。

The unfolded protein response (UPR) is a cellular mechanism that protects cells during stress conditions in which there is an accumulation of misfolded proteins in the endoplasmic reticulum (ER). UPR activates three signaling pathways that function to alleviate stress conditions and promote cellular homeostasis and cell survival. During unmitigated stress conditions, however, UPR activation signaling changes to promote cell death through apoptosis. Interestingly, cancer cells take advantage of this pathway to facilitate survival and avoid apoptosis even during prolonged cell stress conditions. Here, we discuss different signaling pathways associated with UPR and focus specifically on one of the ER signaling pathways activated during UPR, inositol-requiring enzyme 1α (IRE1). The rationale is that the IRE1 pathway is associated with cell fate decisions and recognized as a promising target for cancer therapeutics. Here we discuss IRE1 inhibitors and how they might prove to be an effective cancer therapeutic.© 2023. The Author(s).