Reactive oxygen species: A breath of life or death?
Reactive oxygen species: A breath of life or death?
复制标题
DOI：
10.1158/1078-0432.ccr-06-2082
复制
发表时间：
2007-02-01
影响因子：
11.5
通讯作者：
Meyskens, Frank L., Jr.
中科院分区：
文献类型：
--
作者：
Fruehauf, John P.;Meyskens, Frank L., Jr.
迫切需要对癌细胞特异性生物学途径的新见解，以促进合理靶向治疗的发展。活性氧（ROS）及其在癌细胞对生长因子信号和缺氧的反应中的作用正在成为探索癌症致命弱点的新领域。癌症生长的一个显著且几乎普遍的特征是缺氧。不受调节的细胞增殖导致细胞团的形成，超出静息脉管系统，导致氧气和营养剥夺。由此产生的缺氧触发了一些关键的适应，使癌细胞存活，包括细胞凋亡抑制、葡萄糖代谢改变和血管生成表型。具有讽刺意味的是，最近的研究表明，缺氧刺激线粒体产生增加的ROS，随后激活信号通路，如缺氧诱导因子1 α，促进癌细胞存活和肿瘤生长。由于线粒体是参与化疗诱导细胞凋亡诱导的关键细胞器，线粒体、ROS信号和缺氧条件下生存途径激活之间的关系已成为越来越多研究的主题。对ROS信号传导机制的深入了解可能为促进癌症特异性治疗的发现提供新的途径。临床前和临床评估的药物，修改癌症中的ROS信号提供了一个新的途径进行干预。这篇综述将涵盖ros介导的信号在癌细胞中的最新工作及其作为发育治疗靶点的潜力。
New insights into cancer cell-specific biological pathways are urgently needed to promote development of rationally targeted therapeutics. Reactive oxygen species (ROS) and their role in cancer cell response to growth factor signaling and hypoxia are emerging as verdant areas of exploration on the road to discovering cancer's Achilles heel. One of the distinguishing and near-universal hallmarks of cancer growth is hypoxia. Unregulated cellular proliferation leads to formation of cellular masses that extend beyond the resting vasculature, resulting in oxygen and nutrient deprivation. The resulting hypoxia triggers a number of critical adaptations that enable cancer cell survival, including apoptosis suppression, altered glucose metabolism, and an angiogenic phenotype. Ironically, recent investigations suggest that oxygen depletion stimulates mitochondria to elaborate increased ROS, with subsequent activation of signaling pathways, such as hypoxia inducible factor 1 alpha that promote cancer cell survival and tumor growth. Because mitochondria are key organelles involved in chemotherapy-induced apoptosis induction, the relationship between mitochondria, ROS signaling, and activation of survival pathways under hypoxic conditions has been the subject of increased study. Insights into mechanisms involved in ROS signaling may offer novel avenues to facilitate discovery of cancer-specific therapies. Preclinical and clinical evaluation of agents that modify ROS signaling in cancer offers a novel avenue for intervention. This review will cover recent work in ROS-mediated signaling in cancer cells and its potential as a target for developmental therapeutics.