Sánchez-Álvarez Miguel, Strippoli Raffaele, Donadelli Massimo, Bazhin Alexandr V, Cordani Marco
Mechanoadaptation & Caveolae Biology Lab, Cell and Developmental Biology Area, Centro Nacional de Investigaciones Cardiovasculares (CNIC). Madrid 28029, Spain.
Department of Molecular Medicine, Sapienza University of Rome, Rome 00161, Italy.
Cancers (Basel). 2019 Sep 22;11(10):1415. doi: 10.3390/cancers11101415.
The regulation of Reactive Oxygen Species (ROS) levels and the contribution therein from networks regulating cell metabolism, such as autophagy and the mTOR-dependent nutrient-sensing pathway, constitute major targets for selective therapeutic intervention against several types of tumors, due to their extensive rewiring in cancer cells as compared to healthy cells. Here, we discuss the sestrin family of proteins-homeostatic transducers of oxidative stress, and drivers of antioxidant and metabolic adaptation-as emerging targets for pharmacological intervention. These adaptive regulators lie at the intersection of those two priority nodes of interest in antitumor intervention-ROS control and the regulation of cell metabolism and autophagy-therefore, they hold the potential not only for the development of completely novel compounds, but also for leveraging on synergistic strategies with current options for tumor therapy and classification/stadiation to achieve personalized medicine.
活性氧（ROS）水平的调节以及细胞代谢调节网络（如自噬和mTOR依赖性营养感应途径）在其中的作用，构成了针对几种肿瘤进行选择性治疗干预的主要靶点，因为与健康细胞相比，癌细胞中的这些调节网络发生了广泛的重新布线。在这里，我们讨论了 sestrin 蛋白家族——氧化应激的稳态传感器以及抗氧化和代谢适应的驱动因素——作为新兴的药物干预靶点。这些适应性调节因子处于抗肿瘤干预中两个重要节点的交叉点——ROS 控制以及细胞代谢和自噬的调节——因此，它们不仅具有开发全新化合物的潜力，还具有利用与当前肿瘤治疗和分类/分期选项的协同策略来实现个性化医疗的潜力。
