New molecular targets in radiotherapy: DNA damage signalling and repair in targeted and non-targeted cells.
New molecular targets in radiotherapy: DNA damage signalling and repair in targeted and non-targeted cells.
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DOI：
10.1016/j.ejphar.2009.09.068
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发表时间：
2009-12-25
影响因子：
5
通讯作者：
Prise, Kevin M.
中科院分区：
文献类型：
--
作者：
Burdak-Rothkamm, Susanne;Prise, Kevin M.
电离辐射在治疗中起着关键作用，因为它能够直接诱导 DNA 损伤，特别是导致细胞死亡的 DNA 双链断裂。细胞具有多种试图维持基因组稳定性的修复途径。 DNA 修复蛋白已成为治疗的关键目标，使用小分子抑制剂与放射和/或化疗药物相结合作为增强细胞杀伤的手段。我们对细胞对辐射暴露反应的理解取得了重大进展，这来自于对非靶向效应的观察，其中细胞通过能量依赖性 DNA 损伤的直接后果以外的机制做出反应。其中典型的是旁观者信号传导，其中细胞对其邻居已被辐射的事实做出反应。旁观者细胞表现出 DNA 损伤反应，这与直接受辐射的细胞不同。在旁观者细胞中，ATM 和 Rad3 相关 (ATR) 蛋白激酶依赖性信号传导响应停滞的复制叉，是 DNA 损伤反应的早期事件。 ATM 蛋白激酶在旁观者细胞中的 ATR 下游被激活。这为调节旁观者和修复抑制剂的直接效应提供了差异化方法的潜力，这可能会影响肿瘤的反应和放射治疗期间正常组织的保护。
Ionising radiation plays a key role in therapy due to its ability to directly induce DNA damage, in particular DNA double-strand breaks leading to cell death. Cells have multiple repair pathways which attempt to maintain genomic stability. DNA repair proteins have become key targets for therapy, using small molecule inhibitors, in combination with radiation and or chemotherapeutic agents as a means of enhancing cell killing. Significant advances in our understanding of the response of cells to radiation exposures has come from the observation of non-targeted effects where cells respond via mechanisms other than those which are a direct consequence of energy-dependent DNA damage. Typical of these is bystander signalling where cells respond to the fact that their neighbours have been irradiated. Bystander cells show a DNA damage response which is distinct from directly irradiated cells. In bystander cells, ATM- and Rad3-related (ATR) protein kinase-dependent signalling in response to stalled replication forks is an early event in the DNA damage response. The ATM proteine kinase is activated downstream of ATR in bystander cells. This offers the potential for differential approaches for the modulation of bystander and direct effects with repair inhibitors which may impact on the response of tumours and on the protection of normal tissues during radiotherapy.
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影响因子：
8.8
作者：
Chen, S.;Zhao, Y.;Han, W.;Zhao, G.;Zhu, L.;Wang, J.;Bao, L.;Jiang, E.;Xu, A.;Hei, T. K.;Yu, Z.;Wu, L.
通讯作者：
Wu, L.
DOI：
10.1016/j.mrfmmm.2007.02.005
发表时间：
2007-06-01
影响因子：
2.3
作者：
Kashino, Genro;Suzuki, Keiji;Prise, Kevin M.
通讯作者：
Prise, Kevin M.
影响因子：
5.8
作者：
Cowell, IG;Durkacz, BW;Tilby, MJ
通讯作者：
Tilby, MJ
影响因子：
2.6
作者：
GOODHEAD, DT
通讯作者：
GOODHEAD, DT
影响因子：
8
作者：
Burdak-Rothkamm, S.;Short, S. C.;Prise, K. M.
通讯作者：
Prise, K. M.