Department of Pharmacology, Medical School, Jeonbuk National University, Jeonju 54896, Republic of Korea.
School of Pharmacy and Institute of New Drug Development, Jeonbuk National University, Jeonju 54896, Republic of Korea.
Cells. 2022 Nov 25;11(23):3773. doi: 10.3390/cells11233773.
Cancer cells adapt multiple mechanisms to counter intense stress on their way to growth. Tumor microenvironment stress leads to canonical and noncanonical endoplasmic stress (ER) responses, which mediate autophagy and are engaged during proteotoxic challenges to clear unfolded or misfolded proteins and damaged organelles to mitigate stress. In these conditions, autophagy functions as a cytoprotective mechanism in which malignant tumor cells reuse degraded materials to generate energy under adverse growing conditions. However, cellular protection by autophagy is thought to be complicated, contentious, and context-dependent; the stress response to autophagy is suggested to support tumorigenesis and drug resistance, which must be adequately addressed. This review describes significant findings that suggest accelerated autophagy in cancer, a novel obstacle for anticancer therapy, and discusses the UPR components that have been suggested to be untreatable. Thus, addressing the UPR or noncanonical ER stress components is the most effective approach to suppressing cytoprotective autophagy for better and more effective cancer treatment.
癌细胞通过多种机制来适应其生长过程中的强烈压力。肿瘤微环境应激导致经典和非经典内质网应激（ER）反应，介导自噬，并在蛋白毒性挑战期间被激活，以清除未折叠或错误折叠的蛋白质和受损的细胞器，以减轻应激。在这些情况下，自噬作为一种细胞保护机制发挥作用，其中恶性肿瘤细胞在不利的生长条件下重新利用降解的物质来产生能量。然而，自噬的细胞保护作用被认为是复杂的、有争议的和依赖于背景的；自噬的应激反应被认为支持肿瘤发生和耐药性，这必须得到充分解决。本综述描述了一些重要的发现，这些发现表明在癌症中加速的自噬是一种新的抗癌治疗障碍，并讨论了被认为是无法治疗的 UPR 成分。因此，针对 UPR 或非经典 ER 应激成分是抑制细胞保护性自噬的最有效方法，以实现更好、更有效的癌症治疗。
