Project 2- Radiation Biology

放射生物学项目的重点是放射治疗的有效性可以 提高肿瘤局部控制率和癌症患者存活率。目前有三种不同的方法 为实现这一目标而进行的努力：1)开发与之相结合的药理和生物制剂 放疗和化疗，以改善局部肿瘤控制和防止转移扩散。2) 放射治疗新方法和临床试验的发展。3)身份识别 影响肿瘤对放疗或联合化疗反应的基因决定因素 以及利用酵母菌和哺乳动物的基因进行辐射。对计划成员的研究产生了一个 一系列重要的发现，包括低氧对干细胞分化的调节， 寻找肿瘤缺氧的血清生物标志物，开发肿瘤低氧特异性细胞毒素 治疗，识别对DNA修复和适应压力至关重要的新基因，定义 P53在全球基因组DNA修复中的作用，建立小鼠模型来剖析P53的作用 反式激活与P53靶基因在体内应激反应中的应用 癌症、肝癌、肺癌和前列腺癌，以及开发分子和功能成像技术来 指导放射治疗的实施。代表医学院的23名项目成员和 人文与科学学院的生物科学系非常有动力 开发新的靶向治疗与放射治疗相结合，并得到两个 计划项目赠款和430万美元的NCI资金。在过去的五年中，计划成员 发表论文188篇。在癌症中心的支持下，放射生物学在肿瘤中的作用 免疫、干细胞募集和分化以及功能成像将进一步发展 并扩大了。特别是，癌症中心将极大地帮助翻译许多基于实验室的 研究结果将提高放射治疗的有效性带入临床。

The Program in Radiation Biology is focused on ways in which the effectiveness of radiotherapy can increase local tumor control and survival of cancer patients. Three different approaches are being pursued to achieve this goal: 1) Development of pharmacologic and biologic agents to combine with radiotherapy and chemotherapy to improve local tumor control and prevent metastatic spread. 2) Development of new approaches and clinical trials to administer radiotherapy. 3) The identification of genetic determinants that influence the tumor response to radiation or the combination of chemotherapy and radiation using yeast and mammalian genetics. The research of program members has resulted in a series of important findings that include the regulation of stem cell differentiation by hypoxia, identifying a serum biomarker for tumor hypoxia, developing hypoxic specific cytotoxins for cancer therapy, identifying new genes that are essential for DNA repair and adaptation to stress, defining the role of p53 in global genomic DNA repair, generation of mouse models to dissect the role of p53 transactivation and p53 target genes in in vivo stress responses, the use of radiosurgery to treat pancreatic cancer, liver, lung and prostate cancer, and developing molecular and functional imaging techniques to direct the delivery of radiotherapy. The 23 program members representing the School of Medicine and Department of Biological Sciences in the School of Humanities and Sciences are highly motivated to develop new targeted therapeutics to combine with radiotherapy and are well supported by two program project grants and $4.3 million in NCI funding. During the last five years, the program members published 188 papers. With the support of the Cancer Center, the role of Radiation Biology in tumor immunity, stem cell recruitment and differentiation, and functional imaging will be further developed and expanded. In particular, the Cancer Center will greatly aid in translating many of the laboratorybased findings to increase the effectiveness of radiotherapy into the clinic.