Androgen Receptor Action in Castration Resistant Prostate Cancer
雄激素受体在去势抵抗性前列腺癌中的作用
基本信息
- 批准号:10363638
- 负责人:
- 金额:$ 142.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-05-24 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:Androgen ReceptorAndrogensAutomobile DrivingBasic ScienceBenchmarkingCYP17A1 geneCancer RelapseCastrationCell ProliferationCell SurvivalCellsChromatinClinical ResearchClinical TrialsDataDependenceEZH2 geneEnzymesEpigenetic ProcessEssential GenesFeedbackFoundationsFundingGenesGenetic TranscriptionGoalsGrowthLengthMalignant neoplasm of prostateMediatingMedical CastrationModelingMutationPathogenesisPathway interactionsPatientsPhosphorylationPhosphotransferasesPost-Translational Protein ProcessingPre-Clinical ModelProstate Cancer therapyProtein KinaseRNA SplicingReagentRelapseResearch PersonnelResistanceResourcesRoleTechnologyTestingTherapeuticTimeTranslational ResearchVariantabirateroneantagonistcastration resistant prostate cancerclinically relevantenzalutamidegenetic corepressorhormone therapyinhibitorintratumoral androgenkinase inhibitormenneoplastic cellnovelnovel strategiesoverexpressionpreventprogramsprostate cancer cellreceptor expressionresistance mechanismresponsescreeningsuccesstargeted treatmenttherapeutic targettherapy resistanttumortumor growth
项目摘要
This is a revised competitive renewal application for our P01 entitled “Androgen Receptor Action In Castration
Resistant Prostate Cancer”. The past several years have seen a paradigm shift in prostate cancer (PCa)
therapy, as it is now clear that the androgen receptor (AR) remains active and is a therapeutic target in PCa
that relapses after surgical or medical castration (castration-resistant prostate cancer, CRPC). Previous basic,
translational and clinical research conducted by investigators in this P01 proposal made major contributions to
this paradigm shift by elucidating fundamental mechanisms of AR action and mechanisms of castration-
resistance in patients. The CYP17A1 inhibitor abiraterone, and the AR antagonist enzalutamide, are now
standard second line hormonal therapies for men who relapse after castration. Unfortunately, most men who
respond to these therapies will relapse within 1-2 years. Significantly, while a subset of abiraterone or
enzalutamide-resistant PCa may become AR independent, recent results from investigators in this P01 and
others indicate that most continue to express high levels of AR that appears to be transcriptionally active.
Therefore, a major hypothesis in this proposal is that AR activity still persists and is contributing to tumor
growth in abiraterone and enzalutamide-resistant PCa. Moreover, we hypothesize that adaptations made by
PCa cells in response to AR targeted therapies create vulnerabilities that can be exploited therapeutically.
Hence, overall program goals are to elucidate clinically relevant mechanisms that contribute to CRPC and
abiraterone/enzalutamide-resistance, to identify therapeutic approaches that can overcome these resistance
mechanisms and/or exploit new vulnerabilities, and to assess these therapeutic approaches in preclinical
models that can form foundations for clinical trials. The Projects are as follows: 1) Determining and Exploiting
Mechanisms of AR-Mediated Suppression of Cell, 2) Mechanisms Driving AR Full Length and Splice Variant
Activities and Antagonist Resistance, 3) Protein Kinases Influencing Androgen Receptor in Castrate Resistant
Prostate Cancer, 4) Identification of Essential Genes Underlying AR Activity in Antagonist-Resistant CRPC.
这是我们P01的修订竞争性更新申请,标题为“雄激素受体在阉割中的作用”
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 }}
Steven P. Balk其他文献
Recognition of cluster of differentiation 1 antigens by human CD4−CD8>− cytolytic T lymphocyte
人 CD4−CD8>−细胞毒性 T 淋巴细胞对分化簇 1 抗原簇的识别
- DOI:
10.1038/341447a0 - 发表时间:
1989-10-05 - 期刊:
- 影响因子:48.500
- 作者:
Steven Porcelli;Michael B. Brenner;Julia L. Greenstein;Cox Terhorst;Steven P. Balk;Paul A. Bleicher - 通讯作者:
Paul A. Bleicher
Specific reversal of cytolytic T cell-target cell functional binding is induced by free target cells.
游离靶细胞诱导溶细胞性 T 细胞与靶细胞功能结合的特异性逆转。
- DOI:
10.4049/jimmunol.127.1.51 - 发表时间:
1981 - 期刊:
- 影响因子:4.4
- 作者:
Steven P. Balk;M. Mescher - 通讯作者:
M. Mescher
BH3 mimetics targeting BCL-XL have efficacy in solid tumors with RB1 loss and replication stress
靶向 BCL-XL 的 BH3 模拟物在具有 RB1 缺失和复制应激的实体瘤中具有疗效
- DOI:
10.1038/s41467-025-60238-x - 发表时间:
2025-05-28 - 期刊:
- 影响因子:15.700
- 作者:
Andreas Varkaris;Keshan Wang;Mannan Nouri;Nina Kozlova;Daniel R. Schmidt;Anastasia Stavridi;Seiji Arai;Nicholas Ambrosio;Larysa Poluben;Juan M. Jimenez-Vacas;Daniel Westaby;Juliet Carmichael;Fang Xie;Ines Figueiredo;Lorenzo Buroni;Antje Neeb;Bora Gurel;Nicholas Chevalier;Lisha Brown;Olga Voznesensky;Shao-Yong Chen;Joshua W. Russo;Xin Yuan;Dejan Juric;Himisha Beltran;Johann S. De Bono;Matthew G. Vander Heiden;David J. Einstein;Taru Muranen;Eva Corey;Adam Sharp;Steven P. Balk - 通讯作者:
Steven P. Balk
Inhibiteurs de kinase moelle osseuse sur chromosome x (bmx) et leurs utilisations
X 染色体上的骨摩尔激酶抑制剂 (bmx) 及其用途
- DOI:
- 发表时间:
2013 - 期刊:
- 影响因子:0
- 作者:
Nathanael S. Gray;Steven P. Balk;Qingsong Liu;Sen Chen - 通讯作者:
Sen Chen
BCL2 drives castration resistance in castration-sensitive prostate cancer by orchestrating reciprocal crosstalk between oncogenic pathways
BCL2通过协调致癌通路之间的相互串扰,在去势敏感性前列腺癌中驱动去势抵抗。
- DOI:
10.1016/j.celrep.2025.115779 - 发表时间:
2025-06-24 - 期刊:
- 影响因子:6.900
- 作者:
Rahim Hirani;Subhiksha Nandakumar;Nabila Zaman;Prathiksha Prabhakaraalva;Sarah Ann King;Teja Muralidhar Kalidindi;Romina Ghale;Sai Harisha Rajanala;Deborah C. Fidele;Elisa De Stanchina;Gwo-Shu Mary Lee;Mary Ellen Taplin;Steven P. Balk;Adam G. Sowalsky;Michael J. Morris;Naga Vara Kishore Pillarsetty;Konrad H. Stopsack;Anuradha Gopalan;Lorelei A. Mucci;Natasha Kyprianou;Goutam Chakraborty - 通讯作者:
Goutam Chakraborty
Steven P. Balk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('Steven P. Balk', 18)}}的其他基金
WNT5a/ROR2-Mediated Hippo Pathway Activation in Prostate Cancer
前列腺癌中 WNT5a/ROR2 介导的 Hippo 通路激活
- 批准号:
10734173 - 财政年份:2023
- 资助金额:
$ 142.94万 - 项目类别:
Enhancing the Efficacy of Docetaxel in Prostate Cancer
增强多西紫杉醇治疗前列腺癌的疗效
- 批准号:
10665071 - 财政年份:2022
- 资助金额:
$ 142.94万 - 项目类别:
Prostate Cancer Vulnerabilities to BH3 Mimetic Drugs
前列腺癌对 BH3 模拟药物的脆弱性
- 批准号:
10407648 - 财政年份:2021
- 资助金额:
$ 142.94万 - 项目类别:
Prostate Cancer Vulnerabilities to BH3 Mimetic Drugs
前列腺癌对 BH3 模拟药物的脆弱性
- 批准号:
10279279 - 财政年份:2021
- 资助金额:
$ 142.94万 - 项目类别:
SOX9 Mediation of AR and ERG Driven Prostate Cancer
SOX9 介导 AR 和 ERG 驱动的前列腺癌
- 批准号:
9477598 - 财政年份:2014
- 资助金额:
$ 142.94万 - 项目类别:
SOX9 Mediation of AR and ERG Driven Prostate Cancer
SOX9 介导 AR 和 ERG 驱动的前列腺癌
- 批准号:
8653225 - 财政年份:2014
- 资助金额:
$ 142.94万 - 项目类别:
SOX9 Mediation of AR and ERG Driven Prostate Cancer
SOX9 介导 AR 和 ERG 驱动的前列腺癌
- 批准号:
9269164 - 财政年份:2014
- 资助金额:
$ 142.94万 - 项目类别:
Androgen Receptor Action in Castration Resistant Prostate Cancer
雄激素受体在去势抵抗性前列腺癌中的作用
- 批准号:
8475909 - 财政年份:2013
- 资助金额:
$ 142.94万 - 项目类别:
Project 2: Mechanisms Driving AR Full Length and Splice Variant Activities and Antagonist Resistance
项目 2:驱动 AR 全长和剪接变体活动和拮抗剂耐药性的机制
- 批准号:
10363640 - 财政年份:2013
- 资助金额:
$ 142.94万 - 项目类别:
相似海外基金
Abnormalities in androgens and ovarian markers in reproductive-age racially and ethnically diverse women in a prospective longitudinal cohort
前瞻性纵向队列中不同种族和民族的育龄女性雄激素和卵巢标志物的异常
- 批准号:
10930196 - 财政年份:2023
- 资助金额:
$ 142.94万 - 项目类别:
Nonalcoholic Fatty Liver Disease (NAFLD) in Polycystic Ovary Syndrome: The Role of Androgens on Liver Injury and NAFLD Progression
多囊卵巢综合征中的非酒精性脂肪肝 (NAFLD):雄激素在肝损伤和 NAFLD 进展中的作用
- 批准号:
10735807 - 财政年份:2023
- 资助金额:
$ 142.94万 - 项目类别:
Elucidation of the mechanisms by which cells recognize and respond to different levels of androgens
阐明细胞识别和响应不同水平雄激素的机制
- 批准号:
10418461 - 财政年份:2022
- 资助金额:
$ 142.94万 - 项目类别:
Sexual Differentiation of the Brain and Behaviour: Central and Peripheral Targets of Androgens
大脑和行为的性别分化:雄激素的中枢和外周目标
- 批准号:
RGPIN-2019-04999 - 财政年份:2022
- 资助金额:
$ 142.94万 - 项目类别:
Discovery Grants Program - Individual
Influence of Androgens on Tissue-Specific Lipid Metabolites and Liver Injury in Young Women with NAFLD
雄激素对患有 NAFLD 的年轻女性组织特异性脂质代谢和肝损伤的影响
- 批准号:
10570208 - 财政年份:2022
- 资助金额:
$ 142.94万 - 项目类别:
Paxillin and Androgens in the Regulation of Ovarian Follicle Development
桩蛋白和雄激素在卵巢卵泡发育调节中的作用
- 批准号:
10688086 - 财政年份:2022
- 资助金额:
$ 142.94万 - 项目类别:
Influence of Androgens on Tissue-Specific Lipid Metabolites and Liver Injury in Young Women with NAFLD
雄激素对患有 NAFLD 的年轻女性组织特异性脂质代谢和肝损伤的影响
- 批准号:
10355174 - 财政年份:2022
- 资助金额:
$ 142.94万 - 项目类别:
Defining the impact of androgens on uterine immune cell function during endometrial tissue repair
确定子宫内膜组织修复过程中雄激素对子宫免疫细胞功能的影响
- 批准号:
2744296 - 财政年份:2022
- 资助金额:
$ 142.94万 - 项目类别:
Studentship
Use of novel 11-oxygenated androgens to improve diagnostic accuracy and therapeutics in polycystic ovary syndrome
使用新型 11-含氧雄激素提高多囊卵巢综合征的诊断准确性和治疗效果
- 批准号:
10431620 - 财政年份:2022
- 资助金额:
$ 142.94万 - 项目类别:
Paxillin and Androgens in the Regulation of Ovarian Follicle Development
桩蛋白和雄激素在卵巢卵泡发育调节中的作用
- 批准号:
10525097 - 财政年份:2022
- 资助金额:
$ 142.94万 - 项目类别: