NCI Designated Cancer Center, Sanford-Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA; These authors contributed equally.
NCI Designated Cancer Center, Sanford-Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Trends Pharmacol Sci. 2018 Dec;39(12):1021-1032. doi: 10.1016/j.tips.2018.10.004.
During times of stress, autophagy is a cellular process that enables cells to reclaim damaged components by a controlled recycling pathway. This mechanism for cellular catabolism is dysregulated in cancer, with evidence indicating that cancer cells rely on autophagy in the hypoxic and nutrient-poor microenvironment of solid tumors. Mounting evidence suggests that autophagy has a role in the resistance of tumors to standard-of-care (SOC) therapies. Therefore, there is significant interest in the discovery of small molecules that can safely modulate autophagy. In this review, we describe recent advances in the identification of new pharmacological compounds that modulate autophagy, with a focus on their mode of action, value as probe compounds, and validation as potential therapeutics.
在压力时期，自噬是一种细胞过程，可通过受控的回收途径使细胞回收受损的组件。这种细胞分解代谢的机制在癌症中失调，有证据表明，癌细胞依赖于实体瘤缺氧和营养贫乏的微环境中的自噬。越来越多的证据表明，自噬在肿瘤对标准治疗（SOC）疗法的耐药性中起作用。因此，人们对发现能够安全调节自噬的小分子化合物产生了浓厚的兴趣。在这篇综述中，我们描述了最近在鉴定新的能调节自噬的药理学化合物方面的进展，重点介绍了它们的作用模式、作为探针化合物的价值以及作为潜在治疗剂的验证。
