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努力， 手术和放射肿瘤学的进展，胶质母细胞瘤仍然无法治愈和改善 总体来说，存活率微乎其微。虽然放射治疗仍然是最有效的方法之一 对于胶质母细胞瘤的治疗选择，它不能随着时间的推移而控制疾病。这表明 迫切需要新的联合疗法来改善癌症的放射治疗结果 患有这种疾病的病人。本提案中概述的研究基于一项 这一假设得到了我们广泛的初步数据和发表在 文学。总体假设是，基于生物标记物的药物选择预测了协同作用。 联合治疗对GICs和胶质母细胞瘤大块肿瘤细胞群的致命性，防止 辐射诱导的GBM表型转换，并允许个体化优化 放射治疗。父母拨款的三个目标是用一种 跟踪GIC及其后代的创新工具，同时利用独特的资源和 加州大学洛杉矶分校和NIH/NCI CTEP药物组合提供的专业知识。这项管理工作 对家长资助的补充将增加我们团队的多样性，并将增加单个细胞 下一代测序到AIMS。

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.