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.
项目摘要:
众所周知,DNA损伤反应(DDR)途径的缺陷加速肿瘤发生。
已经致力于靶向有缺陷的DDR途径以改善癌症患者的结果。
这些努力导致FDA批准PARP抑制剂用于治疗携带BRCA 1/2的癌症
基因突变,以及批准用于具有错配修复缺陷的癌症的免疫疗法。而且很多
靶向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,
我们迫切需要了解如何有效地使用这些现有的和新的治疗癌症的方法。
我们现在知道,靶向DDR途径和/或DDR缺陷不仅影响内在肿瘤增殖,
也改变了肿瘤微环境的相互作用。因此,我们正在将DDR研究从体外扩展到体内。
vivo设置。在这个项目中,我们将确定几个重要的DDR基因/蛋白质如何控制
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,我们将
研究体内癌症治疗中DDR缺陷。我们最近在体内CRISPR筛选方面的成功为我们提供了
有机会探索靶向DDR途径和DDR缺陷的途径,用于体内癌症治疗。我们
我预计从这些研究中获得的知识将有助于我们设计更好的癌症治疗策略
患者
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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{{ 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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