Biomarkers of Radiation Exposure: Can They Predict Normal Tissue Radiosensitivity?
Biomarkers of Radiation Exposure: Can They Predict Normal Tissue Radiosensitivity?
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DOI：
10.1016/j.clon.2013.06.010
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发表时间：
2013-10-01
影响因子：
3.4
通讯作者：
Rothkamm, K.
中科院分区：
文献类型：
--
作者：
Chua, M. L. K.;Rothkamm, K.
晚期不良组织反应影响多达五分之一接受放射治疗的癌症患者，已知有几个临床参数会影响正常组织反应。尽管仔细控制了治疗相关参数，但正常组织反应中个体间变异性的重要组成部分仍无法解释，这表明可能内在遗传和表观遗传因素是正常组织效应的主要决定因素。在此背景下，研究开始进入细胞标记物预测临床放射敏感性，首先集中在集落形成测定，可靠的替代终点，如染色体放射敏感性和DNA损伤修复的到来之前。最近，合作努力集中在靶基因或全基因组水平的基因分型分析。尽管测试这些测定的几个小规模试点研究的早期阳性报告，但随后试图在更大的队列中重现细胞标志物和临床表型之间的可比水平的相关性通常是不确定的，尽管第一个重复性良好的研究开始出现。在这里，我们讨论了基本原理，考虑有关患者招募和研究设计方面，审查了一些DNA损伤相关标志物的报告结果，并强调了一些限制和混淆因素影响预测标志物和临床放射敏感性之间的关联测试。我们建议采用一种综合方法，将涉及跨中心合作的多种检测方法与考虑正常组织反应的修改临床因素的患者前瞻性细致招募相结合，提高了找到长期寻求的个体放射敏感性标志物的机会。皇冠版权所有（C）2013由爱思唯尔有限公司代表放射科医师皇家学院发布。All rights reserved.
Late adverse tissue reactions affect up to a fifth of cancer patients receiving radiotherapy, with several clinical parameters known to influence normal tissue responses. Despite careful control of treatment-related parameters, a significant component of inter-individual variability in normal tissue responses remains unaccounted for, suggesting that perhaps intrinsic genetic and epigenetic factors are the major determinants of normal tissue effects. Against this background, research was initiated into cellular markers predictive of clinical radiosensitivity, focusing first on colony-forming assays, before the advent of reliable surrogate end points, such as chromosomal radiosensitivity and DNA damage repair. More recently, collaborative efforts have focused on genotyping analysis at a target gene or whole genome level. Despite early positive reports from several small-scale pilot studies testing these assays, subsequent attempts to reproduce comparable levels of association between the cellular markers and clinical phenotype in larger cohorts have frequently been inconclusive, although the first well-replicated studies are beginning to emerge. Here, we discuss the underlying rationale, consider aspects pertaining to patient recruitment and study design, review some of the reported findings for DNA damage-related markers, and highlight some of the limitations and confounding factors affecting tests of association between predictive markers and clinical radiosensitivity. We propose that an integrative approach incorporating multiple assays involving collaborations across centres, together with prospective meticulous recruitment of patients taking into account modifying clinical factors of normal tissue responses, enhances the chance of finding the long sought after markers of individual radiosensitivity. Crown Copyright (C) 2013 Published by Elsevier Ltd on behalf of The Royal College of Radiologists. All rights reserved.