Cancer cells exploit many of the cellular adaptive responses to support their survival needs. One of these is the unfolded protein response (UPR), a highly conserved signaling pathway that is mounted in response to endoplasmic reticulum (ER) stress. Recent work showed that steroid hormones, in particular estrogens and androgens, regulate the canonical UPR pathways in breast cancer (BCa) and prostate cancer (PCa). In addition, UPR has pleiotropic effects in advanced disease and development of therapy resistance. These findings implicate the UPR pathway as a novel target in hormonally regulated cancers in the clinic. Here, we review the potential therapeutic value of recently developed small molecule inhibitors of UPR in hormone regulated cancers.

癌细胞利用许多细胞适应性反应来支持其生存需求。其中之一是未折叠的蛋白应答（UPR），这是一种高度保守的信号传导途径，响应内质网（ER）应激而建立。最近的研究表明，类固醇激素，尤其是雌激素和雄激素，可调节乳腺癌（BCa）和前列腺癌（PCa）中的经典UPR途径。此外，UPR在晚期疾病和抗药性发展中具有多效作用。这些发现暗示，UPR途径是临床上激素调节型癌症的新靶标。在这里，我们综述了最近开发的UPR小分子抑制剂在激素调节型癌症中的潜在治疗价值。