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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的尽管在基础科学、临床试验、药物开发和技术进步方面付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，总体生存率的改善也微乎其微。虽然放射疗法是胶质母细胞瘤最有效的治疗选择之一，但它无法控制疾病随着时间的推移。这使我们得出结论，迫切需要新的联合疗法来改善患有这种疾病的患者的放射治疗结果。本提案中概述的研究使基于我们广泛的初步数据和文献中发表的数据支持的假设。具体来说，辐射导致分化的神经胶质瘤细胞表型转变为治疗抵抗细胞神经胶质瘤起始细胞（GIC），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创新工具追踪 GIC 来解决神经胶质瘤生物学的这个方面及其后代，并利用加州大学洛杉矶分校的独特资源和专业知识。如果成功的话结果这些研究，特别是目标 2 和 3 将对放射肿瘤学产生更广泛的影响，因为原理不仅适用于胶质母细胞瘤，也适用于许多其他实体癌。