Understanding CDK1 Function and Cancer Vulnerabilities

了解 CDK1 功能和癌症脆弱性

基本信息

  • 批准号:
    10736617
  • 负责人:
  • 金额:
    $ 48.39万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-06-13 至 2028-05-31
  • 项目状态:
    未结题

项目摘要

Project Summary/Abstract Precision therapies for aggressive or metastatic cancers, while offering the promise of greater efficacy and less toxicity, rarely achieve durable responses and only modestly extend a patient's life. The major limitation to these approaches is that cancer cells evolve and alternate signaling pathways can compensate for pathways blocked with targeted therapies, i.e. multiple alternative mechanisms to activate the EGFR/RAS/MAPK pathway lead to a "whack-a-mole" approach with serial treatment with different kinase inhibitors. Cyclin-dependent kinases (CDKs) are a conserved family of protein kinases that play a central role in regulating the eukaryotic cell cycle. CDK1 in conjunction with its activating subunit, Cyclin B, plays a critical role in permitting cells to enter mitosis, coordinates the events required for faithful mitotic progression and chromosome segregation. To our knowledge, CDK1/B activity is essential for all cells to proliferate and there are no alternative pathways to bypass the requirement for CDK1. We hypothesize that CDK1 is an ideal therapeutic target in the context of specific oncogenic signaling pathways which result in an abortive cell cycle program, such as cell death or senescence, while non-tumor cells are only transiently arrested. Until now, specific inhibitors of CDK1 have not existed, limiting our ability to discover the underlying mechanisms of CDK1 inhibition as a cancer therapy. Our lab developed a novel engineered mouse, using a chemical-genetic approach, that allows us to inhibit CDK1 selectively and reversibly in normal and oncogene transformed cells, or in the context of transgenic tumor models. Our aims will define the mechanisms through which CDK1 elicits growth arrest and senescence (Aim 1), regulates the unfolded protein response (Aim 2), and how CDK1 inhibition and other therapeutics can be best combined to block tumor growth (Aim 3). We bring together a team with a track record of innovative research in oncogene signaling and cell cycle regulation (Andrei Goga); expertise in chemical biology and analog-sensitive kinases (Kevan Shokat); in vivo studies of senescence (Anil Bhushan) and expertise in mechanisms of regulation of the unfolded protein response (UPR). We hypothesize that CDK1 controls previously unexplored cellular processes which can be exploited for tumor-specific vulnerabilities. Such discoveries will hasten the clinical translation of CDK1 inhibitors for a broad variety of human cancers.
项目总结/文摘

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 }}

ANDREI GOGA其他文献

ANDREI GOGA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('ANDREI GOGA', 18)}}的其他基金

Understanding breast cancer progression as a defect in the mechanics of tissue self-organization
将乳腺癌进展理解为组织自组织机制的缺陷
  • 批准号:
    10395995
  • 财政年份:
    2020
  • 资助金额:
    $ 48.39万
  • 项目类别:
Understanding breast cancer progression as a defect in the mechanics of tissue self-organization
将乳腺癌进展理解为组织自组织机制的缺陷
  • 批准号:
    10613917
  • 财政年份:
    2020
  • 资助金额:
    $ 48.39万
  • 项目类别:
A single cell assay for tissue activity
组织活性的单细胞测定
  • 批准号:
    10831316
  • 财政年份:
    2020
  • 资助金额:
    $ 48.39万
  • 项目类别:
Uncovering Mechanisms of Regulation and Dependency on Fatty Acid Oxidation in MYC-Driven Tumors
揭示 MYC 驱动肿瘤中脂肪酸氧化的调节和依赖性机制
  • 批准号:
    10194413
  • 财政年份:
    2018
  • 资助金额:
    $ 48.39万
  • 项目类别:
Uncovering Mechanisms of Regulation and Dependency on Fatty Acid Oxidation in MYC-Driven Tumors
揭示 MYC 驱动肿瘤中脂肪酸氧化的调节和依赖性机制
  • 批准号:
    10436804
  • 财政年份:
    2018
  • 资助金额:
    $ 48.39万
  • 项目类别:
In Vivo Metabolic Catastrophe Is Induced By Acute Oncogene Inhibition (PQ #22)
体内代谢灾难是由急性癌基因抑制(PQ
  • 批准号:
    8676483
  • 财政年份:
    2012
  • 资助金额:
    $ 48.39万
  • 项目类别:
In Vivo Metabolic Catastrophe Is Induced By Acute Oncogene Inhibition (PQ #22)
体内代谢灾难是由急性癌基因抑制(PQ
  • 批准号:
    8384577
  • 财政年份:
    2012
  • 资助金额:
    $ 48.39万
  • 项目类别:
In Vivo Metabolic Catastrophe Is Induced By Acute Oncogene Inhibition (PQ #22)
体内代谢灾难是由急性癌基因抑制(PQ
  • 批准号:
    8513950
  • 财政年份:
    2012
  • 资助金额:
    $ 48.39万
  • 项目类别:
Targeting the MYC Oncogene with CDK Inhibitors
使用 CDK 抑制剂靶向 MYC 癌基因
  • 批准号:
    8641666
  • 财政年份:
    2010
  • 资助金额:
    $ 48.39万
  • 项目类别:
Targeting the MYC Oncogene with CDK Inhibitors
使用 CDK 抑制剂靶向 MYC 癌基因
  • 批准号:
    7890072
  • 财政年份:
    2010
  • 资助金额:
    $ 48.39万
  • 项目类别:

相似海外基金

RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 48.39万
  • 项目类别:
    Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 48.39万
  • 项目类别:
    Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 48.39万
  • 项目类别:
    Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 48.39万
  • 项目类别:
    Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 48.39万
  • 项目类别:
    Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 48.39万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 48.39万
  • 项目类别:
    Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
  • 批准号:
    2301846
  • 财政年份:
    2023
  • 资助金额:
    $ 48.39万
  • 项目类别:
    Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 48.39万
  • 项目类别:
    Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
  • 批准号:
    23K16076
  • 财政年份:
    2023
  • 资助金额:
    $ 48.39万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了