Kastan Michael B
Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Blood Cells Mol Dis. 2007 Sep-Oct;39(2):148-50. doi: 10.1016/j.bcmd.2007.04.002. Epub 2007 May 29.
Significant progress has been made in recent years elucidating the molecular controls of cellular responses to DNA damage in mammalian cells. Many of the insights that we have gained into the mechanisms involved in cellular DNA damage response pathways have come from studies of human cancer susceptibility syndromes that are altered in DNA damage responses. ATM, the gene mutated in the cancer-prone disorder, ataxia telangiectasia, is a protein kinase that is a central mediator of responses to DNA double strand breaks in cells. Such insights provide us with opportunities to develop new approaches to benefit patients. For example, inhibitors of the ATM pathway have the potential to act as sensitizers to chemotherapy or radiation therapy and could even have anti-neoplastic effects on their own. Conversely, activators of ATM could improve responses to cellular stresses such as oxidative damage. The potential benefits of ATM modulation in disease settings ranging from metabolic syndrome to cancer will be discussed.
近年来，在阐明哺乳动物细胞对DNA损伤的细胞反应的分子控制方面取得了重大进展。我们对细胞DNA损伤反应途径所涉及机制的许多见解都来自对DNA损伤反应发生改变的人类癌症易感性综合征的研究。ATM是一种在易患癌症的疾病——共济失调毛细血管扩张症中发生突变的基因，它是一种蛋白激酶，是细胞对DNA双链断裂反应的核心介质。这些见解为我们提供了开发使患者受益的新方法的机会。例如，ATM途径的抑制剂有可能作为化疗或放疗的增敏剂，甚至自身可能具有抗肿瘤作用。相反，ATM的激活剂可以改善对细胞应激（如氧化损伤）的反应。将讨论在从代谢综合征到癌症等疾病背景下调节ATM的潜在益处。
