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Chronotherapy for glioblastoma

胶质母细胞瘤的时间疗法

基本信息

批准号：
10318540
负责人：
Erik Herzog
金额：
$ 19.69万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-12-15 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10318540
关键词：
Adverse event Affect Area Behavior Brain Neoplasms Cancer Etiology Caring Cells Cessation of life Chronotherapy Circadian Rhythms Circadian gene expression Clinical Clinical Trials Collaborations Colorectal Cancer Cytotoxic Chemotherapy DNA Damage DNA Repair Pathway Data Disease Diurnal Rhythm Dose Engineering Epigenetic Process Event Evolution Female Future Gene Expression Genetic Genetic Engineering Genotype Glioblastoma Growth Implant In Vitro Individual Investigation Malignant Glioma Malignant neoplasm of brain Modeling Molecular Mus Myelosuppression Oncologist Pathway interactions Patient Agents Patients Pattern Phenotype Publications Reporter Research Role Testing Therapeutic Time Translations Tumor Biology Variant Work Xenograft Model Xenograft procedure antitumor effect cancer care cancer stem cell chemotherapy circadian circadian biology clinical care colon cancer treatment genotypic sex improved improved outcome in vivo in vivo evaluation individual variation leukemia male neoplastic cell neuro-oncology novel novel therapeutics response side effect standard care success temozolomide therapy resistant translational applications translational impact tumor tumor ablation tumor growth tumor heterogeneity tumor microenvironment tumorigenesis

项目摘要

Project Summary This proposal tests the fundamental hypothesis that circadian rhythms in brain tumors provide a temporal therapeutic window during which the efficacy of standard treatments may be substantially optimized. Timed delivery of chemotherapy, or chronotherapy, has an established role in colorectal cancer and leukemia but has never been evaluated in brain tumors. Here we build on exciting preliminary data in which we have demonstrated that the efficacy of Temozolomide (TMZ), an established chemotherapeutic for glioblastoma (GBM) is substantially modulated by the time of day when it is administered. These findings suggest that we may already have the means of significantly improving outcome from this dismal disease. In this proposal we will utilize novel intracranial xenograft models of GBM in which tumor cells have been engineered to serve as reporters of tumor circadian time, and in which recipient mice have been genetically engineered to represent four different patterns of diurnal variations in behavior, or chronotype. We will test in vivo, whether GBM cells maintain stable circadian rhythms, whether these are independent or entrained by the host, whether treatment with TMZ is best optimized to tumor or host circadian rhythm and whether there is therapeutic value in ablating tumor circadian rhythm. Success in these studies will advance our basic understanding of GBM circadian biology and will provide critical information for the translational application of chronotherapy to GBM care.

项目总结