Glioblastoma, Glioblastoma Stem Cells and Radiotherapy

摘要 尽管在基础科学、临床试验、药物开发和技术进步方面做出了巨大努力 放射肿瘤学方面，胶质母细胞瘤仍然无法治愈，总体存活率的改善微乎其微。 虽然放射治疗是胶质母细胞瘤最有效的治疗方法之一，但它不能控制这种疾病。 随着时间的推移。这导致我们得出结论，迫切需要新的联合疗法来改进 患有这种疾病的患者的放射治疗结果。这项提案中概述的研究使 都是基于一个假设，该假设得到了我们广泛的初步数据和文献中公布的数据的支持。 具体地说，辐射导致分化的胶质瘤细胞表型转化为耐药 胶质瘤启动细胞(GICs)和干扰这一过程将提高放射治疗的效率。 这项研究的三个目标将利用一种追踪GIC的创新工具来解决胶质瘤生物学的这一方面 以及他们的后代，并利用加州大学洛杉矶分校提供的独特资源和专业知识。如果成功，则结果 这些研究，特别是目标2和目标3将对放射肿瘤学产生更广泛的影响，因为这些 原则不仅适用于胶质母细胞瘤，也适用于许多其他实体癌症。

Abstract Despite a tremendous effort in basic science, clinical trials, drug development, and technical advances in radiation oncology, glioblastoma remains incurable and improvements in overall survival have been marginal. While radiotherapy is one of the most effective treatment options for glioblastoma it cannot control the disease over time. This led us to conclude that novel combination therapies are desperately needed to improve radiation treatment outcome for patients suffering from this disease. The studies outlined in this proposal make are base on a hypothesis that is backed by our extensive preliminary data and published data in the literature. Specifically, that radiation causes a phenotype conversion of differentiated glioma cells into therapy-resistant glioma-initiating cells (GICs) and that interfering with this process will increase the efficiency of radiotherapy. The three aims of this study will address this aspect of glioma biology using an innovative tool to track GICs and their progeny and make use of unique resources and expertise available at UCLA. If successful, results from these studies and in particular Aim 2 and 3 will have wider impact on radiation oncology as these principles apply not only to glioblastoma but many other solid cancer.