CHD1 and TAK1 Synthetic Lethality in Prostate Cancer
CHD1 和 TAK1 在前列腺癌中的综合致死率
基本信息
- 批准号:8873686
- 负责人:
- 金额:$ 16.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-04-06 至 2017-03-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAndrogen AntagonistsAntineoplastic AgentsApoptosisBar CodesBiological ModelsBladderBreastCell Cycle ProgressionCell modelCellsChromosomal RearrangementCollaborationsColon LymphomaComplexControl GroupsDNA Sequence AlterationDNA Sequence RearrangementDNA-Binding ProteinsDU145DataDependenceDiseaseEpigenetic ProcessExploratory/Developmental GrantFunding MechanismsFutureGene AmplificationGene DeletionGenesGeneticGenomeGenomic DNAGoalsGrowthHarvestHealthHistonesHumanHuman GeneticsIn VitroInfectionLNCaPLeadLesionLibrariesLinkMAP Kinase Kinase KinaseMAP3K7 geneMalignant NeoplasmsMalignant neoplasm of prostateMutateMutationPARP inhibitionPC3 cell linePI3K/AKTPTEN genePathway interactionsPhosphotransferasesPoly(ADP-ribose) PolymerasesPrimary NeoplasmProstateProstatic NeoplasmsProteinsProto-Oncogene Proteins c-aktPublishingReadingRecurrenceRegimenResearchResistanceRoleSignal PathwayTestingThe Cancer Genome AtlasTherapeuticTransforming Growth Factor betaTumor Suppressor ProteinsVariantWorkXenograft procedurebasebiological adaptation to stresscancer genomicscell motilityclinically relevantcytokinedeep sequencinggenome-widehelicasehigh riskin vivoin vivo Modelinhibitor/antagonistkillingsmennovelpersonalized medicinephase II trialprostate cancer cellpublic health relevancerepairedsmall hairpin RNAtargeted sequencingtherapeutic targettranslational approachtumortumorigenesis
项目摘要
DESCRIPTION (provided by applicant): Prostate cancer is a complex disease characterized by recurrent gene deletions and amplifications. Human genetic data demonstrate correlation between dual loss of CHD1 and MAP3K7 with lethal prostate cancer. We recently showed in both published and unpublished data that MAP3K7 and CHD1 loss leads to aggressive castrate-resistant prostate cancer. We did this with two independent model systems providing strong support for the overall conclusions of the studies that provide a functional link between these two novel tumor suppressors and prostate cancer aggressiveness. Because MAP3K7 and CHD1 are both tumor suppressors, and by definition lost or inactivated in prostate cancer, neither are directly targetable with therapeutic strategies. We hypothesize that cells with loss of
MAP3K7 and CHD1 have dependence on novel survival pathways and we propose to exploit these pathways to kill tumors that have lost MAP3K7 and/or CHD1. We will use two complementary approaches to identify therapeutic vulnerabilities. In Aim 1 we will screen human prostate cells with knockdown of CHD1 and/or MAP3K7 for the ability of common prostate cancer drugs to inhibit growth and tumorigenesis in vitro and in vivo. In aim 2 we will use a genome-wide shRNA screen to identify synthetic lethal targets in cells with loss of MAP3K7 and/or CHD1. This is a high-risk, high-gain project appropriate for an R21 type funding mechanism. Each aim is independent and each needs to be done. Together the two aims will define potential therapeutic approaches to an extremely aggressive variant of prostate cancer.
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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Scott D Cramer其他文献
Pancreatic cancer cells express 25-hydroxyvitamin D-1 alpha-hydroxylase and their proliferation is inhibited by the prohormone 25-hydroxyvitamin D3.
胰腺癌细胞表达 25-羟基维生素 D-1 α-羟化酶,其增殖受到激素原 25-羟基维生素 D3 的抑制。
- DOI:
- 发表时间:
2004 - 期刊:
- 影响因子:4.7
- 作者:
Gary G. Schwartz;D. Eads;Anuradha Rao;Scott D Cramer;Mark C. Willingham;Tai;Daniel P. Jamieson;Lilin Wang;K. Burnstein;M. Holick;Constantinos Koumenis - 通讯作者:
Constantinos Koumenis
Scott D Cramer的其他文献
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{{ truncateString('Scott D Cramer', 18)}}的其他基金
Androgen Signaling in CaP with loss of MAP3K7 and CHD1
MAP3K7 和 CHD1 缺失的 CaP 中的雄激素信号转导
- 批准号:
10657393 - 财政年份:2021
- 资助金额:
$ 16.9万 - 项目类别:
Androgen Signaling in CaP with loss of MAP3K7 and CHD1
MAP3K7 和 CHD1 缺失的 CaP 中的雄激素信号转导
- 批准号:
10276486 - 财政年份:2021
- 资助金额:
$ 16.9万 - 项目类别:
Androgen Signaling in CaP with loss of MAP3K7 and CHD1
MAP3K7 和 CHD1 缺失的 CaP 中的雄激素信号转导
- 批准号:
10439892 - 财政年份:2021
- 资助金额:
$ 16.9万 - 项目类别:
Autophagy regulation of prostate tumor development
自噬调节前列腺肿瘤的发展
- 批准号:
9096644 - 财政年份:2016
- 资助金额:
$ 16.9万 - 项目类别:
CHD1 and MAP3K7 coordinate deletion in aggressive ERG translocation negative prostate cancer
CHD1 和 MAP3K7 在侵袭性 ERG 易位阴性前列腺癌中协调缺失
- 批准号:
9265055 - 财政年份:2015
- 资助金额:
$ 16.9万 - 项目类别:
CHD1 and MAP3K7 coordinate deletion in aggressive ERG translocation negative prostate cancer
CHD1 和 MAP3K7 在侵袭性 ERG 易位阴性前列腺癌中协调缺失
- 批准号:
9090060 - 财政年份:2015
- 资助金额:
$ 16.9万 - 项目类别:














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