Molecular anatomy of radiation hypersensitivity

放射治疗(RT)是一种根治性的抗癌治疗，约有一半的癌症患者接受了放射治疗。偶尔，癌症患者会对RT表现出意想不到的不良反应，有强有力的证据表明这种RT敏感性是有遗传基础的。尽管进行了20年的研究，但目前无法在治疗前预测此类反应，它们的发生限制了大多数患者的RT强度，从而限制了治愈率。该项目将使用尖端技术(DNA芯片或微阵列)来试图了解为什么一些患者会出现显著的RT副作用，而绝大多数患者没有。我们已经开发了一个来自有不良RT反应的癌症患者的样本的组织库，这些样本(以及来自未受影响的癌症患者的样本)将通过微阵列进行检查：在每个实验中将评估数千个基因的活性，我们将寻找跟踪RT敏感性的基因活性模式。如果我们确定一种模式，这一模式将与更多的病例进行对照，如果它准确地预测了放射治疗的敏感性，可能会导致癌症患者在接受放射治疗之前进行常规测试，并实现癌症治疗的个体化。同时，我们将使用能够检测辐射反应异常的分析方法来评估敏感患者的组织，这可能为潜在的基因缺陷(S)提供线索，该缺陷可能易于对辐射敏感。

Radiotherapy (RT) is a curative anti-cancer treatment employed in around half of all cancer sufferers. Very occasionally, a cancer patient will manifest an unexpected adverse reaction to RT and there is strong evidence for a genetic basis to such RT sensitivity. Despite two decades of research, such reactions cannot currently be predicted prior to treatment and their occurrence limits the intensity, and hence cure rates, of RT for the majority of patients. This project will employ cutting edge technology (DNA Chips, or microarrays) to attempt to understand why some patients suffer significant RT side-effects, while the vast majority do not. We have developed a tissue bank of samples from cancer patients who have had adverse RT reactions, and these samples (and samples from unaffected cancer patients) will be examined by microarrays: the activity of thousands of genes will be evaluated in each experiment, and we shall search for patterns of gene activity which track with RT sensitivity. Should we determine a pattern, this pattern will be checked against a larger number of cases and if it accurately predicts RT sensitivity, could lead to the routine testing of cancer patients prior to RT and the individualisation of cancer therapy. In parallel, we will evaluate the tissues of sensitive patients with assays capable of detecting abnormalities in the response to radiation, which may give clues as to an underlying gene fault(s) which might predispose to radiosensitivity in that individual.