Screening for DNA damage response modulators in glioblastoma stem cells
胶质母细胞瘤干细胞中 DNA 损伤反应调节剂的筛选
基本信息
- 批准号:10038588
- 负责人:
- 金额:$ 42万
- 依托单位:
- 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:2020-09-15 至 2022-07-31
- 项目状态:已结题
- 来源:
- 关键词:AcidosisAdjuvantAdjuvant TherapyAlkylating AgentsAlternative TherapiesBiological AssayBiological ProcessBloodBrain NeoplasmsCell DeathCell SurvivalCellsCellular StressChemotherapy and/or radiationConditioned Culture MediaDNADNA DamageDNA Double Strand BreakDNA RepairDNA Sequence AnalysisDoseDouble Strand Break RepairDrug ScreeningDrug TargetingEnvironmentEnzymesEventExcisionExperimental Animal ModelFatty Acid DesaturasesGeneticGlioblastomaGliomaHypoxiaImpairmentLeftLibrariesLuciferasesMalignant - descriptorMalignant NeoplasmsMeasuresMediatingMolecular ProfilingMonitorNonhomologous DNA End JoiningNormal CellNutrientOperative Surgical ProceduresPathway interactionsPatientsPharmaceutical ChemistryPharmaceutical PreparationsPharmacologyPhasePopulationPrimary Brain NeoplasmsProliferatingProteinsQuality of lifeRad51 recombinaseRadiation therapyRecurrenceReporterReportingResistanceResistance developmentSystemTestingTherapeuticTimeTreatment Efficacyanalogbasecancer stem cellchemoradiationconventional therapydesigngenotoxicityhigh throughput screeninginhibitor/antagonistneoplastic cellnoveloutcome forecastoxidative DNA damagepatient variabilityradioresistantrepairedresponsescreeningsmall moleculestem cellsstem-like celltemozolomidetherapy resistanttumorvirtual
项目摘要
Abstract
There is presently no cure for high grade gliomas which are associated with a bleak prognosis
and a poor quality of life. GBM patients typically undergo surgical resection followed by radiation
therapy (RT) combined with the alkylating agent temozolomide (TMZ). However, virtually all GBM
patients either fail to respond to this treatment, or ultimately develop resistance, underlining the
urgency for effective adjuvant therapies. Both RT and TMZ can target tumor cells by causing
lethal DNA double-strand breaks, which could be recognized and repaired by the intrinsic DNA
damage response (DDR) thus protecting against DNA damage-induced cell death. Further, GBMs
are enriched in a subset population of glioma cancer stem cells (GSCs), characterized by an
upregulated DDR which contributes to their superior therapeutic resistance. Targeting DNA repair
can increase/restore sensitivity of brain tumors to TMZ and RT, thus increasing therapeutic
efficacy and minimizing tumor recurrence. We have designed a rapid, versatile and highly
sensitive reporter that can detect and quantify minute amounts of DNA double-strand break
repairs such as homology-directed repair as well as non-homologous end joining without
disrupting cells. Here we propose to use this reporter in order to identify modulators of DNA
damage repair in GSCs. In Aim 1 (R61 phase), we will develop and optimize a high-throughput
screening assay to monitor DDR in GSCs. In Aim 2 (R33 phase), we will use this assay to screen
for compounds which inhibit DNA damage repair. Upon completion of this project, this screen
should identify novel compounds which effectively sensitize GSCs to chemoradiotherapy and
increase the efficacy of genotoxic therapeutics.
摘要
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Christian Elias Badr其他文献
Christian Elias Badr的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Christian Elias Badr', 18)}}的其他基金
Translocon-regulated ER proteostasis in glioblastoma
胶质母细胞瘤中易位蛋白调节的内质网蛋白稳态
- 批准号:
10301296 - 财政年份:2021
- 资助金额:
$ 42万 - 项目类别:
Role of ER Stress and Fatty Acid Metabolism in Glioma Stem Cells
内质网应激和脂肪酸代谢在胶质瘤干细胞中的作用
- 批准号:
10665639 - 财政年份:2020
- 资助金额:
$ 42万 - 项目类别:
Role of ER stress and fatty acid metabolism in glioma stem cells
内质网应激和脂肪酸代谢在胶质瘤干细胞中的作用
- 批准号:
10261413 - 财政年份:2020
- 资助金额:
$ 42万 - 项目类别:
Role of ER stress and fatty acid metabolism in glioma stem cells
内质网应激和脂肪酸代谢在胶质瘤干细胞中的作用
- 批准号:
10461146 - 财政年份:2020
- 资助金额:
$ 42万 - 项目类别:
Screening for DNA Damage Response Modulators in Glioblastoma Stem Cells
胶质母细胞瘤干细胞中 DNA 损伤反应调节剂的筛选
- 批准号:
10683338 - 财政年份:2020
- 资助金额:
$ 42万 - 项目类别:
Screening for DNA damage response modulators in glioblastoma stem cells
胶质母细胞瘤干细胞中 DNA 损伤反应调节剂的筛选
- 批准号:
10618739 - 财政年份:2020
- 资助金额:
$ 42万 - 项目类别:
Identifying vulnerabilities and therapeutic targets in Glioma Stem Cells
识别神经胶质瘤干细胞的脆弱性和治疗靶点
- 批准号:
8948656 - 财政年份:2015
- 资助金额:
$ 42万 - 项目类别:
相似海外基金
Countering sympathetic vasoconstriction during skeletal muscle exercise as an adjuvant therapy for DMD
骨骼肌运动期间对抗交感血管收缩作为 DMD 的辅助治疗
- 批准号:
10735090 - 财政年份:2023
- 资助金额:
$ 42万 - 项目类别:
The ESCAPE clinical trial of circulating tumor DNA to guide adjuvant therapy in chemo-resistant triple negative breast cancer
循环肿瘤 DNA 指导化疗耐药三阴性乳腺癌辅助治疗的 ESCAPE 临床试验
- 批准号:
494901 - 财政年份:2023
- 资助金额:
$ 42万 - 项目类别:
Operating Grants
A Type I Hybrid Effectiveness-Implementation Trial to Evaluate a Navigation-Based Multilevel Intervention to Decrease Delays Starting Adjuvant Therapy Among Patients with Head and Neck Cancer
一项 I 型混合有效性实施试验,用于评估基于导航的多级干预措施,以减少头颈癌患者开始辅助治疗的延迟
- 批准号:
10714537 - 财政年份:2023
- 资助金额:
$ 42万 - 项目类别:
Multi-modal machine learning to guide adjuvant therapy in surgically resectable colorectal cancer
多模式机器学习指导可手术切除结直肠癌的辅助治疗
- 批准号:
10588103 - 财政年份:2023
- 资助金额:
$ 42万 - 项目类别:
Efficacy of ethanol adjuvant therapy after resection of malignant soft tissue tumors
恶性软组织肿瘤切除术后乙醇辅助治疗的疗效
- 批准号:
22K09407 - 财政年份:2022
- 资助金额:
$ 42万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of immune response cells and development of novel adjuvant therapy for sublingual immunotherapy
免疫应答细胞的鉴定和舌下免疫治疗新型辅助疗法的开发
- 批准号:
21KK0287 - 财政年份:2022
- 资助金额:
$ 42万 - 项目类别:
Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
Pursuing molecular biomarkers to guide adjuvant therapy for HPV+ head and neck cancers after transoral robotic surgery
寻找分子生物标志物来指导经口机器人手术后 HPV 头颈癌的辅助治疗
- 批准号:
10357120 - 财政年份:2022
- 资助金额:
$ 42万 - 项目类别:
Biomarker research using two prospective studies on preoperative and postoperative adjuvant therapy for pancreatic cancer
使用两项关于胰腺癌术前和术后辅助治疗的前瞻性研究进行生物标志物研究
- 批准号:
21K08700 - 财政年份:2021
- 资助金额:
$ 42万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Personalized Resistant Starch as an Adjuvant Therapy for Pediatric Inflammatory Bowel Disease
个性化抗性淀粉作为小儿炎症性肠病的辅助治疗
- 批准号:
437315 - 财政年份:2020
- 资助金额:
$ 42万 - 项目类别:
Studentship Programs
Tailored adjuvant therapy in POLE-mutated and p53-wildtype early stage endometrial cancer (TAPER)
POLE 突变和 p53 野生型早期子宫内膜癌 (TAPER) 的定制辅助治疗
- 批准号:
435603 - 财政年份:2020
- 资助金额:
$ 42万 - 项目类别:
Operating Grants