Use of CTEP portfolio compounds to counteract phenotype conversion in GBM

使用 CTEP 组合化合物来抵消 GBM 中的表型转换

基本信息

批准号：
10598714
负责人：
Frank Pajonk
金额：
$ 5.42万
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：
2022
资助国家：
美国
起止时间：
2022-01-01 至 2026-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10598714
关键词：
3-Dimensional Address Administrative Supplement Affect Back Basic Science Biological Assay Biological Markers Biology Cancer Therapy Evaluation Program Cell Differentiation process Cell physiology Cells Cholesterol Clinical Clinical Trials Clonal Evolution Combined Modality Therapy Data Disease Dose Drug Kinetics Electromagnetic Energy Fatty Acids Gene Expression Profiling Generations Glioblastoma Glioma Goals Hypoxia In Vitro Lead Level of Evidence Literature Malignant Neoplasms Malignant neoplasm of brain Metabolic Modality Modeling Nitric Oxide Operative Surgical Procedures Pathway interactions Patient-Focused Outcomes Patients Pharmaceutical Preparations Phenotype Population Process Publishing Radiation Radiation Dose Unit Radiation Oncology Radiation therapy Recurrence Reporting Resources Scheme Specimen Testing Time Toxic effect Transgenic Mice Treatment Failure United States National Institutes of Health base blood-brain barrier crossing cancer stem cell chemotherapeutic agent chemotherapy cholesterol biosynthesis disorder control drug development effective therapy imaging system improved in vivo induced pluripotent stem cell inhibitor innovation malignant breast neoplasm mevalonate mouse model neoplastic cell nerve stem cell nestin protein neurogenesis next generation sequencing novel parent grant prevent radiation resistance radioresistant responders and non-responders self-renewal standard of care stem cells synergism targeted agent temozolomide therapy outcome therapy resistant tool trait tumor

项目摘要

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.

摘要/摘要尽管在基础科学、临床试验、药物开发和技术方面付出了巨大努力手术和放射肿瘤学的进步，胶质母细胞瘤仍然无法治愈和改进总体生存率已经微乎其微。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，它无法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该假设得到了我们广泛的初步数据和严格发表的数据的支持文学。总体假设是基于生物标志物的药物选择可以预测协同作用联合疗法对 GIC 和胶质母细胞瘤大量肿瘤细胞群的致死率，可预防辐射诱导的 GBM 表型转换，并允许个性化优化放射治疗。家长资助的三个目标是利用以下方法解决神经胶质瘤生物学的这个方面：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 (UCLA) 和 NIH/NCI CTEP 药物组合提供专业知识。本次行政对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达到目标。