Use of CTEP portfolio compounds to counteract phenotype conversion in GBM

摘要/摘要 尽管在基础科学、临床试验、药物开发和技术方面做出了巨大的努力， 随着外科手术和放射肿瘤学的进步，胶质母细胞瘤仍然是不可治愈的， 总体存活率是微不足道的。虽然放射治疗仍然是最有效的治疗方法之一， 胶质母细胞瘤的治疗选择，它不能随着时间的推移控制疾病。这表明 迫切需要新的联合疗法来改善放射治疗结果， 患有这种疾病的患者。本提案中概述的研究基于 这一假设得到了我们广泛的初步数据和严格的已发表数据的支持， 文学总的假设是，基于生物标志物的药物选择预测协同 联合治疗在GIC和胶质母细胞瘤大量肿瘤细胞群中的致死性， 辐射诱导的GBM表型转换，并允许个体化优化 放疗母基金的三个目标是使用一种 跟踪GIC及其后代的创新工具，同时利用独特的资源， UCLA和NIH/NCI CTEP药物组合的专业知识。这一行政 家长补助金的补充将增加我们团队的多样性，并将增加单细胞 下一代测序的目标。

Summary/Abstract Despite a tremendous effort in basic science, clinical trials, drug development, and technical advances in surgery and radiation oncology, glioblastoma remains incurable and improvements in overall survival have been marginal. While radiotherapy is still one of the most effective treatment options for glioblastoma, it cannot control the disease over time. This suggests that novel combination therapies are desperately needed to improve radiation treatment outcome for patients suffering from this disease. The studies outlined in this proposal are based on a hypothesis that is backed by our extensive preliminary data and rigorous published data in the literature. The overall hypothesis is that biomarker-based drug selection predicts synergistic lethality of combination therapies in GICs and glioblastoma bulk tumor cell populations, prevents radiation-induced GBM phenotype conversion and allows for individualized optimization of radiotherapy. The three aims of the parent grant address this aspect of glioma biology using an innovative tool to track GICs and their progeny, while leveraging the unique resources and expertise available at UCLA and the NIH/NCI CTEP portfolio of drugs. This administrative supplement to the parent grant will increase the diversity of our team and will add single cell next generation sequencing to the aims.