Zhang Lijuan, Zhu Yuxuan, Zhang Jiahui, Zhang Lan, Chen Lu
Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Personalized Drug Therapy Key Laboratory of Sichuan Province, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Front Pharmacol. 2022 Aug 11;13:966012. doi: 10.3389/fphar.2022.966012. eCollection 2022.
Autophagy is a self-degradation process in which damaged proteins and organelles are engulfed into autophagosomes for digestion and eventually recycled for cellular metabolism to maintain intracellular homeostasis. Accumulating studies have reported that autophagy has the Janus role in cancer as a tumor suppressor or an oncogenic role to promote the growth of established tumors and developing drug resistance. Importantly, cytoprotective autophagy plays a prominent role in many types of human cancers, thus inhibiting autophagy, and has been regarded as a promising therapeutic strategy for cancer therapy. Here, we focus on summarizing small-molecule compounds inhibiting the autophagy process, as well as further discuss other dual-target small-molecule compounds, combination strategies, and other strategies to improve potential cancer therapy. Therefore, these findings will shed new light on exploiting more small-molecule compounds inhibiting cytoprotective autophagy as candidate drugs for fighting human cancers in the future.
自噬是一种自我降解过程,在此过程中,受损的蛋白质和细胞器被吞噬进自噬体进行消化,最终被循环用于细胞代谢以维持细胞内稳态。越来越多的研究报道,自噬在癌症中具有双重作用,既作为肿瘤抑制因子,又具有致癌作用,可促进已形成肿瘤的生长并产生耐药性。重要的是,细胞保护性自噬在多种人类癌症中发挥着重要作用,因此抑制自噬已被视为一种有前景的癌症治疗策略。在此,我们着重总结抑制自噬过程的小分子化合物,并进一步讨论其他双靶点小分子化合物、联合策略以及其他改善潜在癌症治疗的策略。因此,这些发现将为未来开发更多抑制细胞保护性自噬的小分子化合物作为对抗人类癌症的候选药物提供新的思路。