权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Differential response of glioblastomas to microtubule targeting agents

胶质母细胞瘤对微管靶向剂的差异反应

基本信息

批准号：
10208829
负责人：
Nephi Stella
金额：
$ 35.57万
依托单位：
UNIVERSITY OF WASHINGTON
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：
2020-07-02 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10208829
关键词：
Address Apoptosis Behavior Binding Biological Assay Biological Models Blood - brain barrier anatomy Brain Cancer cell line Carbazoles Cell Culture Techniques Cell Cycle Cell Survival Cell division Cells Chromosomal Instability Colchicine Collaborations Coupled DNA Damage Data Development Diagnosis Exhibits Foundations Genetic Glioblastoma Goals Grant Growth Hematologic Neoplasms Image Laboratories Link Malignant - descriptor Measures Microscopy Microtubules Mitosis Modeling Molecular Mus Non-Malignant Oncogenic Patients Penetrance Pharmacology Platelet-Derived Growth Factor Property Radiation therapy Radiation-Sensitizing Agents Radiosensitization Reporting Research Project Grants Series Site Solid TP53 gene Testing Therapeutic Time Treatment Efficacy Tubulin Work Xenograft procedure base cancer cell cancer type cell motility experimental study genetic approach in vivo in vivo Model innovative technologies insight learning algorithm live cell imaging live cell microscopy migration mouse model novel novel therapeutics pre-clinical response side effect standard care standard of care targeted agent temozolomide treatment response tumor tumorigenesis

项目摘要

Microtubule targeting agents (MTAs) are commonly prescribed to treat many types of cancers; yet their use for the treatment of glioblastomas (GBM) is limited by their poor brain penetrance. We developed a new series of MTAs (ST-compounds) that destabilize microtubules (MT) and kill GBM through a novel mechanism of action (MOA). Our recent results show that ST-compounds pass the blood brain barrier (BBB) and exhibits in vivo therapeutic efficacy in a preclinical mouse model of GBM. This new R01 uses complementary expertise and approaches to study how the novel MOA of ST- compounds differs from known MTAs and its therapeutic efficacy in several preclinical mouse model of GBM. Specifically, it leverages several innovative technologies, including live-cell imaging and artificial learning algorithms, to better understand why GBM are particularly sensitive to the antitumor activity of ST-compounds. Experiments will be performed on patient-derived GBM (PD-GBM) in culture and include measure of real-time changes in GBM cell migration, cell division and cell cycle fate as fundamental readouts of tumorigenesis. In vivo experiments will be done on both genetic orthotopic mouse models of GBM and orthotopic mouse model of PD-GBM. Our aims are: 1: Differential impact of MTAs on the migration and mitosis of GBM in culture. 2: Differential impact of MTAs on the viability and fate of GBM in culture. 3: Therapeutic efficacy and mechanism of ST-401 in GBM models in vivo. Our immediate goal is to increase our understanding of the precise MOA by which MTAs regulate GBM tumorigenesis and how this interacts with standard care treatments. This work will help set a solid foundation for the development of a new class of MTAs for the safe treatment of patients diagnosed with GBM.

微管靶向药物（mta）通常用于治疗多种类型的癌症；然而他们对