Evaluation of Novel Radiation Modifiers

许多代理商已经开始为这个项目进行测试。一种名为MEK抑制剂的试剂已被评估为体外和体内的辐射增敏剂。该试剂被发现在体外使三个组织对辐射敏感，并在皮下异种移植中使两个受试细胞系对辐射敏感。更多的机制研究表明，这种敏感化的原因似乎与辐射后G2检查点的废除有关。该化合物的其他工作集中在可能的生物标志物上，以确定临床翻译疗效的候选标志物。此外，该制剂与化疗联合使用，并观察到对辐射的额外增敏作用，支持进行临床试验。以我为主要研究员的这种化合物开始了一项临床试验。这些化合物的最终目标是将其转化为辐射增敏剂的临床试验。此外，PI一直在积极地将辐射生物学分部合作者的研究成果转化为非临床试验。

A number of agents have begun testing for this project. One agent, a MEK inhibitor, has been evaluated as a radiation sensitizer both in vitro and in vivo. The agent was found to sensitize three histologies to radiation in vitro and to sensitize two tested cell lines to radiation in subcutaneous xenografts. Additional mechanistic work has revealed that the cause of this senstization appears to be related to abrogation of the G2 checkpoint after irradiation. Additional work with this compound is focusing on possible biomarkers of effect to identify candidate markers of efficacy for clinical translation. In addition, the agent was comined with chemotherapy and additional sensitization to radiation was seen, supporting the conduct of a clinical trial. A clinical trial was initiated with this compound with myself as the Pricipal Investigator.The eventual goal for these compounds is clinical translation into trials as radiation sensitizers. In additon, the PI has been active in translating findings from collaborators in the Radiation Biology Branch inot clinical trials.