Oncopharmacology Unit, Centre Antoine Lacassagne, 33 avenue Valombrose, 06100 Nice, France.
Cancer Treat Rev. 2012 Oct;38(6):737-59. doi: 10.1016/j.ctrv.2012.02.004. Epub 2012 Mar 2.
More than half of cancer patients are treated by radiation therapy, with a wide inter-patient variability in tumour response. Recent advances have been made in understanding molecular mechanisms that govern the behaviour of tumour cells and tissues exposed to ionizing radiation. Accumulating data suggest an important role of DNA damage response genes, including DNA repair (especially double-strand breaks), apoptosis and cell-cycle control genes. It has been hypothesized that frequent germinal polymorphisms, most often single-nucleotide polymorphisms, in DNA damage response genes may impact tumour response and clinical outcome for patients receiving a radiotherapy-based treatment. We reviewed literature covering the relationships between candidate gene polymorphisms in DNA damage response and the efficacy of a radiation-based treatment. Although several methodological limitations may preclude a definitive conclusion, single nucleotide polymorphisms of several candidate genes such as ERCC- or XRCC-family genes seem to be potential predictive biomarkers of radiotherapy efficacy, even though not strictly involved in radiotherapy-induced double-strand breaks repair. In order to improve the relevance of clinical results, and our interpretation of them, we draw a parallel between clinical findings and available preclinical data on polymorphism functionality. Clinical findings require validation in larger replication studies and open the prospect of future clinical trials.
超过一半的癌症患者接受放射治疗，肿瘤反应在患者间存在广泛的变异性。近年来，人们在理解控制肿瘤细胞和组织对电离辐射行为的分子机制方面取得了进展。越来越多的证据表明，DNA 损伤反应基因（包括 DNA 修复（尤其是双链断裂）、细胞凋亡和细胞周期控制基因）起着重要作用。人们假设，DNA 损伤反应基因中的常见生殖系多态性（通常是单核苷酸多态性）可能会影响接受基于放射治疗的患者的肿瘤反应和临床结局。我们回顾了涵盖 DNA 损伤反应候选基因多态性与基于放射治疗的疗效之间关系的文献。尽管存在一些方法学限制，可能无法得出明确的结论，但 ERCC 或 XRCC 家族基因等几个候选基因的单核苷酸多态性似乎是放射治疗疗效的潜在预测生物标志物，尽管它们与放射诱导的双链断裂修复并无严格关系。为了提高临床结果的相关性以及我们对这些结果的解释，我们将临床发现与可用的关于多态性功能的临床前数据进行了比较。临床发现需要在更大的复制研究中进行验证，并为未来的临床试验开辟了前景。
