Exploring DNA damage response pathways as targets for cancer therapy
探索 DNA 损伤反应途径作为癌症治疗的目标
基本信息
- 批准号:10515484
- 负责人:
- 金额:$ 58.34万
- 依托单位:
- 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:2022-09-01 至 2029-08-31
- 项目状态:未结题
- 来源:
- 关键词:AffectBRCA mutationsCRISPR screenCancer PatientCell Cycle CheckpointCell ProliferationClinical TrialsDNA DamageDNA RepairDefectDevelopmentGene ProteinsGenesGenomic InstabilityGoalsImmune TargetingIn VitroKnowledgeMismatch Repair DeficiencyMutationPathway interactionsanticancer treatmentcancer immunotherapycancer therapydesigngene repairimmune checkpointimproved outcomein vivoinhibitornovel therapeuticsresponsesuccesstargeted cancer therapytreatment strategytumortumor microenvironmenttumorigenesis
项目摘要
Project Summary:
It is well established that defects in DNA damage response (DDR) pathways accelerate tumorigenesis.
Significant efforts have been devoted to target defective DDR pathways to improve outcome for cancer patients.
These efforts led to the FDA’s approval of PARP inhibitors for the treatment of cancers carrying BRCA1/2
mutations and also the approval of immunotherapy for cancers with mismatch repair deficiency. Moreover, many
inhibitors targeting DNA repair and/or cell cycle checkpoints have also entered clinical trials. Thus, there is an
urgent need to understand how to effectively use these existing and new therapies for cancer treatment.
We now know that targeting DDR pathways and/or DDR defects not only affect intrinsic tumor proliferation, but
also change tumor-microenvironment interactions. Thus, we are expanding our DDR studies from in vitro to in
vivo settings. In this project, we will determine mechanistically how several essential DDR genes/proteins control
cell proliferation and DNA damage repair. We plan to establish separation of function mutations to further
elucidate the key roles of these DDR genes and pathways both in vitro and in vivo. Additionally, we will
investigate DDR defects in cancer therapy in vivo. Our recent success with in vivo CRISPR screens provides us
an opportunity to explore avenues to target DDR pathways and DDR defects for cancer treatment in vivo. We
anticipate that knowledge gained from these studies will help us design better treatment strategies for cancer
patients.
项目总结:
众所周知,DNA损伤反应(DDR)通路的缺陷会加速肿瘤的发生。
已经致力于针对有缺陷的DDR通路来改善癌症患者的预后。
这些努力导致FDA批准PARP抑制剂用于治疗携带BRCA1/2的癌症
突变,以及对错配修复缺陷癌症的免疫治疗的批准。此外,许多人
针对DNA修复和/或细胞周期检查点的抑制剂也已进入临床试验。因此,有一个
迫切需要了解如何有效地将这些现有的和新的疗法用于癌症治疗。
我们现在知道,靶向DDR通路和/或DDR缺陷不仅影响固有的肿瘤增殖,而且
也改变了肿瘤与微环境的相互作用。因此,我们正在将我们的DDR研究从体外扩展到
VIVO设置。在这个项目中,我们将机械地确定几个必需的DDR基因/蛋白质是如何控制的
细胞增殖和DNA损伤修复。我们计划建立功能突变分离,以进一步
阐明这些DDR基因和途径在体外和体内的关键作用。此外,我们还将
研究体内肿瘤治疗中的DDR缺陷。我们最近在活体CRISPR筛查方面的成功为我们提供了
有机会探索针对体内癌症治疗的DDR通路和DDR缺陷的途径。我们
预计从这些研究中获得的知识将帮助我们设计更好的癌症治疗策略
病人。
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)
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Junjie Chen其他文献
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{{ truncateString('Junjie Chen', 18)}}的其他基金
Deciphering pathways involved in topoisomerase II turnover
破译拓扑异构酶 II 周转涉及的途径
- 批准号:
10552113 - 财政年份:2023
- 资助金额:
$ 58.34万 - 项目类别:
Elucidating mechanisms underlying replication checkpoint control
阐明复制检查点控制的底层机制
- 批准号:
10620981 - 财政年份:2023
- 资助金额:
$ 58.34万 - 项目类别:
Define redundant functions of H2AX and NBS1 in DNA repair
定义DNA修复中H2AX和NBS1的冗余功能
- 批准号:
10311996 - 财政年份:2017
- 资助金额:
$ 58.34万 - 项目类别:
Project 4: Coordinating Nucleolytic Pathways During Crosslink Repair
项目 4:在交联修复过程中协调溶核途径
- 批准号:
9148677 - 财政年份:2017
- 资助金额:
$ 58.34万 - 项目类别:
Define redundant functions of H2AX and NBS1 in DNA repair
定义DNA修复中H2AX和NBS1的冗余功能
- 批准号:
9206732 - 财政年份:2017
- 资助金额:
$ 58.34万 - 项目类别:
Define redundant functions of H2AX and NBS1 in DNA repair
定义DNA修复中H2AX和NBS1的冗余功能
- 批准号:
10053713 - 财政年份:2017
- 资助金额:
$ 58.34万 - 项目类别:
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