McGrath Eoghan P, Logue Susan E, Mnich Katarzyna, Deegan Shane, Jäger Richard, Gorman Adrienne M, Samali Afshin
Apoptosis Research Centre, National University of Ireland (NUI), Galway, University Road, Galway, H91 TK33 Galway, Ireland.
School of Natural Sciences, NUI Galway, University Road, H91 TK33 Galway, Ireland.
Cancers (Basel). 2018 Sep 21;10(10):344. doi: 10.3390/cancers10100344.
In 2018, in the US alone, it is estimated that 268,670 people will be diagnosed with breast cancer, and that 41,400 will die from it. Since breast cancers often become resistant to therapies, and certain breast cancers lack therapeutic targets, new approaches are urgently required. A cell-stress response pathway, the unfolded protein response (UPR), has emerged as a promising target for the development of novel breast cancer treatments. This pathway is activated in response to a disturbance in endoplasmic reticulum (ER) homeostasis but has diverse physiological and disease-specific functions. In breast cancer, UPR signalling promotes a malignant phenotype and can confer tumours with resistance to widely used therapies. Here, we review several roles for UPR signalling in breast cancer, highlighting UPR-mediated therapy resistance and the potential for targeting the UPR alone or in combination with existing therapies.
据估计,仅在2018年,美国就有268,670人将被诊断出患有乳腺癌,其中41,400人将死于该病。由于乳腺癌常常会对治疗产生耐药性,并且某些乳腺癌缺乏治疗靶点,因此迫切需要新的治疗方法。一种细胞应激反应途径——未折叠蛋白反应(UPR),已成为开发新型乳腺癌治疗方法的一个有前景的靶点。该途径在内质网(ER)稳态受到干扰时被激活,但具有多种生理功能和疾病特异性功能。在乳腺癌中,UPR信号传导促进恶性表型,并可使肿瘤对广泛使用的疗法产生耐药性。在此,我们综述了UPR信号传导在乳腺癌中的几种作用,重点介绍了UPR介导的治疗耐药性以及单独靶向UPR或与现有疗法联合靶向UPR的潜力。