Project 2: TOPK/PRPK as Novel Targets for Skin Cancer Prevention
项目2:TOPK/PRPK作为皮肤癌预防新靶点
基本信息
- 批准号:10686370
- 负责人:
- 金额:$ 16万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-10 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AccountingActinic keratosisApoptosisApoptosis InhibitorAttenuatedBasal cell carcinomaBreastBromidesCancer Cell GrowthCancer EtiologyCell Culture TechniquesCell LineCell physiologyCellsCessation of lifeChemopreventionChronicColorectalDangerousnessDataDevelopmentDistantEffectivenessEnvironmental CarcinogensEpidermisFDA approvedFamilyFusidic AcidGeneral PopulationGenesGrowthHealthHumanIncidenceInflammationInflammatory ResponseKRP proteinKnock-outLegal patentLightLungLymphokine-Activated Killer CellsLymphomaMEKsMalignant NeoplasmsMedicalMitogen-Activated Protein Kinase KinasesModelingMorbidity - disease rateMusNeoplasm MetastasisNeoplastic Cell TransformationOncogenicOperative Surgical ProceduresPathway interactionsPharmaceutical PreparationsPhosphotransferasesPlayPreventionPreventiveProliferatingProstaglandin ProductionProstaglandinsProtein KinaseProtein-Serine-Threonine KinasesProteinsRas/RafRisk FactorsRoleSignal PathwaySignal TransductionSignaling MoleculeSiteSkinSkin CancerSkin CarcinogenesisSkin CarcinomaStimulation of Cell ProliferationSunlightSunscreening AgentsSystemTP53 geneTestingTimeTopical applicationTumor Cell InvasionTumor PromotersUV Radiation ExposureUV inducedUltraviolet Raysclinical implementationcyclooxygenase 2diagnostic biomarkerdraining lymph nodeeffectiveness testingimprovedin vivoinhibitorkeratinocyteleukemiamelanomamembermortalitymouse modelneoplastic cellnovelnovel diagnosticsp53 related protein kinasepharmacologicpremalignantpreventprogramsprotein kinase inhibitorskin cancer preventionskin lesionskin squamous cell carcinomasolar ultraviolet radiationsunlight-inducedsurvivintherapeutic developmenttumortumor growthultraviolet
项目摘要
ABSTRACT
Project 2 (Dong, Bode) TOPK/PRPK as Novel Targets for Skin Cancer Prevention
Solar ultraviolet (sUV) light is an environmental carcinogen that causes inflammation and cancer. Notably, the
incidence of non-melanoma skin cancer (NMSC) is increasing yearly. Reducing the incidence of cutaneous
squamous cell carcinomas (cSCCs) would not only reduce their potentially severe morbidity and mortality, but
also dramatically reduce the multibillion dollar health bill associated with surgical and medical treatments
required for NMSCs. Thus identifying the signaling molecules in the development of cSCC is critically important.
We recently discovered 2 new very promising protein targets for preventing sUV-induced skin cancer and will
focus on those kinases in this renewal working with Projects 1 and 3. The T-LAK cell-originated protein kinase
(TOPK), a serine-threonine kinase, is a member of the mitogen-activated protein kinase kinase (MAPKK) family,
and is involved in tumor development, growth, apoptosis, and inflammation. TOPK is highly expressed in a
variety of cancers, including NMSCs and melanoma. We also found that p53-related protein kinase (PRPK),
which is downstream of TOPK, is a crucial player in skin cancer development. This project is aimed to examine
the role of TOPK and PRPK in SSL-induced skin cancer and to test the effectiveness of novel TOPK and PRPK
inhibitors in preventing sUV-induced skin cancer. The hypothesis to be tested in this proposal is that TOPK and
PRPK play functional roles in SSL-induced skin carcinogenesis and are novel diagnostic markers and important
targets for the development of therapeutic agents to prevent and treat NMSCs. Because our preliminary data
showed that targeting TOPK or PRPK can almost totally block solar UV-induced skin cancer, we expect that data
from this project have the potential to completely negate the idea that skin cancer cannot be prevented.
摘要
项目2(Dong,Bode)TOPK/PRPK作为皮肤癌预防的新靶点
太阳紫外线(sUV)是一种环境致癌物质,可导致炎症和癌症。特别是
非黑色素瘤皮肤癌(NMSC)的发病率逐年增加。减少皮肤病的发生率
鳞状细胞癌(cSCC)不仅可以降低其潜在的严重发病率和死亡率,
还可以大大减少与手术和医疗相关的数十亿美元的医疗费用,
需要NMSC。因此,识别cSCC发展中的信号分子至关重要。
我们最近发现了两个新的非常有前途的蛋白质靶点,用于预防sUV诱导的皮肤癌,
在项目1和项目3的更新工作中,重点关注这些激酶。T-LAK细胞源性蛋白激酶
丝氨酸-苏氨酸激酶(TOPK)是丝裂原活化蛋白激酶激酶(MAPKK)家族的成员,
并参与肿瘤的发展、生长、凋亡和炎症。TOPK在一种
各种癌症,包括NMSC和黑色素瘤。我们还发现p53相关蛋白激酶(PRPK),
它是TOPK的下游,是皮肤癌发展的关键因素。该项目旨在研究
TOPK和PRPK在SSL诱导的皮肤癌中的作用,并测试新的TOPK和PRPK的有效性
抑制剂预防sUV诱导的皮肤癌。本提案中要检验的假设是,TOPK和
PRPK在SSL诱导的皮肤癌发生中发挥功能性作用,是新的诊断标志物,
用于开发预防和治疗NMSC的治疗剂的靶点。因为我们的初步数据
显示靶向TOPK或PRPK几乎可以完全阻断太阳紫外线诱导的皮肤癌,我们预计数据
从这个项目有可能完全否定的想法,皮肤癌不能预防。
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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REBECCA Jane MORRIS其他文献
REBECCA Jane MORRIS的其他文献
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{{ truncateString('REBECCA Jane MORRIS', 18)}}的其他基金
Project 2: TOPK/PRPK as Novel Targets for Skin Cancer Prevention
项目2:TOPK/PRPK作为皮肤癌预防新靶点
- 批准号:
10475138 - 财政年份:2019
- 资助金额:
$ 16万 - 项目类别:
Project 2: TOPK/PRPK as Novel Targets for Skin Cancer Prevention
项目2:TOPK/PRPK作为皮肤癌预防新靶点
- 批准号:
10252870 - 财政年份:2019
- 资助金额:
$ 16万 - 项目类别:
Project 2: TOPK/PRPK as Novel Targets for Skin Cancer Prevention
项目2:TOPK/PRPK作为皮肤癌预防新靶点
- 批准号:
10015217 - 财政年份:2019
- 资助金额:
$ 16万 - 项目类别:
Identification of a Keratinocyte Stem Cell Regulatory Gene in the KSC2 Locus
KSC2 基因座中角质形成细胞干细胞调节基因的鉴定
- 批准号:
8707971 - 财政年份:2012
- 资助金额:
$ 16万 - 项目类别:
Identification of a Keratinocyte Stem Cell Regulatory Gene in the KSC2 Locus
KSC2 基因座中角质形成细胞干细胞调节基因的鉴定
- 批准号:
8235740 - 财政年份:2012
- 资助金额:
$ 16万 - 项目类别:
Identification of a Keratinocyte Stem Cell Regulatory Gene in the KSC2 Locus
KSC2 基因座中角质形成细胞干细胞调节基因的鉴定
- 批准号:
8508187 - 财政年份:2012
- 资助金额:
$ 16万 - 项目类别:
The Role of Bone Marrow Derived Cells in Skin Cancer
骨髓来源细胞在皮肤癌中的作用
- 批准号:
7787632 - 财政年份:2010
- 资助金额:
$ 16万 - 项目类别:
The Role of Bone Marrow Derived Cells in Skin Cancer
骨髓来源细胞在皮肤癌中的作用
- 批准号:
8016702 - 财政年份:2010
- 资助金额:
$ 16万 - 项目类别:
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