Radiogenomics: A systems biology approach to understanding genetic risk factors for radiotherapy toxicity?
Radiogenomics: A systems biology approach to understanding genetic risk factors for radiotherapy toxicity?
复制标题
放射基因组学：一种了解放射疗法毒性遗传危险因素的系统生物学方法？
DOI：
10.1016/j.canlet.2016.02.035
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发表时间：
2016-11-01
期刊：
影响因子：
9.7
通讯作者：
West, Catharine M. L.
中科院分区：
文献类型：
--
作者：
Herskind, Carsten;Talbot, Christopher J.;Kerns, Sarah L.;Veldwijk, Marlon R.;Rosenstein, Barry S.;West, Catharine M. L.
关键词：
放射治疗（RT）后正常组织中的不良反应限制了可以给予肿瘤细胞的剂量。由于临床应答中80%的个体差异估计是由患者相关因素引起的，因此识别这些因素可能有助于预测发生重度反应风险增加的患者。虽然细胞更新的失活被认为是早期反应正常组织中毒性的主要原因，但涉及多种细胞类型、细胞因子和缺氧的复杂相互作用似乎对晚期反应很重要。在这里，我们回顾“组学”的方法，如筛选遗传多态性或基因表达分析，并评估表观遗传因素，翻译后修饰，信号转导和代谢的潜力。此外，功能测定表明可能与不良反应的临床风险相关。结合不同的“组学”方法的途径分析可能比基于单一“组学”数据集的途径分析更有效地识别关键途径。将这些途径与功能测定相结合，可能有助于识别以不同机制为特征的RT患者的多个亚组。因此，“组学”和功能的方法可能会协同作用，如果他们被整合到放射基因组学“系统生物学”，以促进个性化放射治疗的目标。
Adverse reactions in normal tissue after radiotherapy (RT) limit the dose that can be given to tumour cells. Since 80% of individual variation in clinical response is estimated to be caused by patient-related factors, identifying these factors might allow prediction of patients with increased risk of developing severe reactions. While inactivation of cell renewal is considered a major cause of toxicity in early-reacting normal tissues, complex interactions involving multiple cell types, cytokines, and hypoxia seem important for late reactions. Here, we review ‘omics’ approaches such as screening of genetic polymorphisms or gene expression analysis, and assess the potential of epigenetic factors, posttranslational modification, signal transduction, and metabolism. Furthermore, functional assays have suggested possible associations with clinical risk of adverse reaction. Pathway analysis incorporating different ‘omics’ approaches may be more efficient in identifying critical pathways than pathway analysis based on single ‘omics’ data sets. Integrating these pathways with functional assays may be powerful in identifying multiple subgroups of RT patients characterized by different mechanisms. Thus ‘omics’ and functional approaches may synergize if they are integrated into radiogenomics ‘systems biology’ to facilitate the goal of individualised radiotherapy.
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