摘要
遗传毒性的抗癌药物影响DNA损伤,从而引起信号转导的网络调节称为DNA损伤反应(DDR)。共济失调毛细血管扩张症突变基因(ATM)蛋白在这一反应中起主要的作用:被 DNA损伤激活,ATM的磷酸化和阻滞细胞周期里DNA修复的下游效应,或诱导细胞凋亡过于严重而无以恢复的DNA损伤。ATM是值得研究的为肿瘤放疗和化疗增敏作用的靶点。过去几年里,制药行业和研究工作实验室已经开发出了一系列的小分子,能够抑制ATM和增强其特异性。一些临床前研究已经表明,这些抑制剂单独使用或配合其他治疗方法可能会提高治疗效果。在本文中我们讨论了ATM抑制剂的进展,关注最近的具有潜在抗肿瘤作用的药物。
关键词: 共济失调毛细血管扩张症突变基因(ATM),化疗,神经胶质瘤,抑制剂,放疗,抵抗,致敏作用
Current Drug Targets
Title:Targeting the Ataxia Telangiectasia Mutated Protein in Cancer Therapy
Volume: 17 Issue: 2
Author(s): Donatella Vecchio and Guido Frosina
Affiliation:
关键词: 共济失调毛细血管扩张症突变基因(ATM),化疗,神经胶质瘤,抑制剂,放疗,抵抗,致敏作用
摘要: Genotoxic anticancer drugs explicate their effects damaging DNA, thus triggering a coordinated signal-transduction network called DNA Damage Response (DDR). Ataxia Telangiectasia Mutated (ATM) protein plays a central role in this response: activated by DNA damage, ATM phosphorylates itself and downstream effectors that arrest cell cycle allowing for DNA repair or, should DNA damage be too severe and not retrievable, inducing apoptosis. ATM is a worth-investigating target for tumor radio- and chemosensitization. During last years, pharmaceutical industries and research laboratories have developed a series of small molecules, capable to inhibit ATM with increasing specificity. Several preclinical studies have demonstrated that these inhibitors alone or in association with other treatments may improve therapeutic outcomes. In this review we discuss ATM inhibitors so far developed, focussing on recent acquisitions on their potential antineoplastic usefulness.
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Cite this article as:
Donatella Vecchio and Guido Frosina , Targeting the Ataxia Telangiectasia Mutated Protein in Cancer Therapy, Current Drug Targets 2016; 17 (2) . https://dx.doi.org/10.2174/1389450115666141110154621
DOI https://dx.doi.org/10.2174/1389450115666141110154621 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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