MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China.
Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Tianhe District, 55 Zhongshan Avenue West, Guangzhou, 510631, China.
J Hematol Oncol. 2020 Nov 25;13(1):159. doi: 10.1186/s13045-020-01000-2.
Inhibiting cell survival and inducing cell death are the main approaches of tumor therapy. Autophagy plays an important role on intracellular metabolic homeostasis by eliminating dysfunctional or unnecessary proteins and damaged or aged cellular organelles to recycle their constituent metabolites that enable the maintenance of cell survival and genetic stability and even promotes the drug resistance, which severely limits the efficacy of chemotherapeutic drugs. Currently, targeting autophagy has a seemingly contradictory effect to suppress and promote tumor survival, which makes the effect of targeting autophagy on drug resistance more confusing and fuzzier. In the review, we summarize the regulation of autophagy by emerging ways, the action of targeting autophagy on drug resistance and some of the new therapeutic approaches to treat tumor drug resistance by interfering with autophagy-related pathways. The full-scale understanding of the tumor-associated signaling pathways and physiological functions of autophagy will hopefully open new possibilities for the treatment of tumor drug resistance and the improvement in clinical outcomes.
抑制细胞存活和诱导细胞死亡是肿瘤治疗的主要方法。自噬通过消除功能失调或不必要的蛋白质以及受损或衰老的细胞细胞器来回收其组成代谢物，从而在细胞内代谢稳态中发挥重要作用，这使细胞存活和遗传稳定性得以维持，甚至促进了耐药性，这严重限制了化疗药物的疗效。目前，针对自噬的治疗似乎具有抑制和促进肿瘤存活的矛盾作用，这使得针对自噬的作用对耐药性的影响更加复杂和模糊。在这篇综述中，我们总结了新兴方法对自噬的调节、靶向自噬对耐药性的作用以及通过干扰自噬相关途径治疗肿瘤耐药性的一些新的治疗方法。全面了解与肿瘤相关的信号通路和自噬的生理功能，有望为治疗肿瘤耐药性和改善临床疗效开辟新的可能性。
