Glioblastoma, Glioblastoma Stem Cells and Radiotherapy

胶质母细胞瘤、胶质母细胞瘤干细胞和放射治疗

• 批准号: 9196164
• 负责人: Frank Pajonk
• 金额: $ 37.08万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-03 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9196164
• 关键词: Address; Affect; Back; Basic Science; Biology; Cells; Clinical; Clinical Trials; Clonal Evolution; Combined Modality Therapy; Data; Disease; Dopamine Antagonists; Dose; Electromagnetic Energy; Failure; Gene Expression; Generations; Glioblastoma; Glioma; Goals; Human; Hypoxia; In Vitro; Literature; Malignant Neoplasms; Mesenchymal; Modality; Modeling; Molecular Profiling; Nitric Oxide; Outcome; Patients; Phenotype; Population; Process; Progression-Free Survivals; Public Health; Publishing; Radiation; Radiation Oncology; Radiation therapy; Radioresistance; Reporting; Resistance; Resources; Sampling; Solid; Specimen; Stem cells; Testing; The Cancer Genome Atlas; Time; Treatment Failure; Treatment outcome; abstracting; base; cancer stem cell; disorder control; drug development; effective therapy; imaging system; improved; in vivo; inhibitor/antagonist; innovation; killings; mouse model; novel; prevent; radiation response; radioresistant; radiosensitive; relating to nervous system; small molecule libraries; therapy outcome; therapy resistant; tool; trait; treatment response; tumor

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.

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， 在放射肿瘤学中，胶质母细胞瘤仍然是不可治愈的，并且总体存活率的改善是微不足道的。 虽然放射治疗是胶质母细胞瘤最有效的治疗选择之一，但它不能控制疾病 随着时间这使我们得出结论，迫切需要新的联合疗法来改善 放射治疗对患有这种疾病的患者的效果。该提案中概述的研究使 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发表的数据的支持。 具体地说，辐射导致分化的神经胶质瘤细胞表型转化为治疗抗性的胶质瘤细胞。 神经胶质瘤起始细胞（GIC），干扰这一过程将增加放射治疗的效率。 本研究的三个目的将使用一种创新的工具来跟踪GIC， 及其后代，并利用加州大学洛杉矶分校的独特资源和专业知识。如果成功，结果 这些研究，特别是目标2和3将对放射肿瘤学产生更广泛的影响， 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。