Targeting inflammatory pathways for tumor radiosensitization.
Targeting inflammatory pathways for tumor radiosensitization.
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以炎症途径为靶点，实现肿瘤放射增敏。
DOI：
10.1016/j.bcp.2010.06.039
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发表时间：
2010-12-15
影响因子：
5.8
通讯作者：
Krishnan, Sunil
中科院分区：
文献类型：
--
作者：
Deorukhkar, Amit;Krishnan, Sunil
尽管放射疗法（RT）是治疗患有许多类型癌症的患者的组成部分，但对RT的细胞毒性作用的固有和/或获得性抗性越来越被认为是有效癌症治疗的显著障碍。固有抗性由组成性激活的致癌、增殖和抗凋亡蛋白/途径介导，而获得性抗性是指辐射暴露后蛋白/途径的瞬时诱导。为了实现RT的全部潜力，有必要了解介导诱导辐射抗性的信号通路，这是一种表征不佳的现象，并确定可用于放射增敏的药物靶点。电离辐射通过激活许多促生存途径在哺乳动物细胞中诱导多层信号传导反应，这些途径会聚以瞬时激活一些重要的转录因子（TF），包括核因子κ B（NF-κB）和信号转导和转录激活因子（STAT），它们是炎症和致癌信号传导的中心介质。总之，这些TF激活广泛的促存活基因，调节炎症、抗凋亡、侵袭和血管生成途径，从而赋予肿瘤细胞放射抗性。同样，辐射诱导的促炎细胞因子网络（包括白细胞介素（IL）-1β、IL-6和肿瘤坏死因子-α）的激活已被证明可介导癌症患者的症状负担（疼痛、疲劳、局部炎症）。因此，靶向辐射诱导的炎症途径可以发挥增强肿瘤放射反应和减少正常组织副作用的双重作用，从而增加癌症治疗的治疗窗口。我们回顾了最近的数据，这些数据表明炎症途径在癌症进展和辐射反应调节中发挥着关键作用。
Although radiation therapy (RT) is an integral component of treatment of patients with many types of cancer, inherent and/or acquired resistance to the cytotoxic effects of RT is increasingly recognized as a significant impediment to effective cancer treatment. Inherent resistance is mediated by constitutively activated oncogenic, proliferative and anti-apoptotic proteins/pathways whereas acquired resistance refers to transient induction of proteins/pathways following radiation exposure. To realize the full potential of RT, it is essential to understand the signaling pathways that mediate inducible radiation resistance, a poorly characterized phenomenon, and identify druggable targets for radiosensitization. Ionizing radiation induces a multi-layered signaling response in mammalian cells by activating many pro-survival pathways that converge to transiently activate a few important transcription factors (TFs), including nuclear factor kappa B (NF-κB) and signal transducers and activators of transcription (STATs), the central mediators of inflammatory and carcinogenic signaling. Together, these TFs activate a wide spectrum of pro-survival genes regulating inflammation, anti-apoptosis, invasion and angiogenesis pathways, which confer tumor cell radioresistance. Equally, radiation-induced activation of pro-inflammatory cytokine network (including interleukin (IL)-1β, IL-6 and tumor necrosis factor-α) has been shown to mediate symptom burden (pain, fatigue, local inflammation) in cancer patients. Thus, targeting radiation-induced inflammatory pathways may exert a dual effect of accentuating the tumor radioresponse and reducing normal tissue side-effects, thereby increasing the therapeutic window of cancer treatment. We review recent data demonstrating the pivotal role played by inflammatory pathways in cancer progression and modulation of radiation response.
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影响因子：
2.2
作者：
Bold, RJ;Virudachalam, S;McConkey, DJ
通讯作者：
McConkey, DJ
影响因子：
6.7
作者：
Balkwill, F.;Mantovani, A.
通讯作者：
Mantovani, A.
影响因子：
3.9
作者：
Bijnsdorp, Irene V.;van den Berg, Jaap;Sminia, Peter
通讯作者：
Sminia, Peter
影响因子：
11.5
作者：
Begley, Jonathan;Ribas, Antoni
通讯作者：
Ribas, Antoni
DOI：
10.1016/0360-3016(89)90103-x
发表时间：
1989-09-01
影响因子：
7
作者：
BENTZEN, SM;OVERGAARD, M;THAMES, HD
通讯作者：
THAMES, HD