Targeted Prevention for Non-Melanoma Skin Cancer
非黑色素瘤皮肤癌的针对性预防
基本信息
- 批准号:10410013
- 负责人:
- 金额:$ 23.45万
- 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:Actinic keratosisAcuteAdjuvantAgeAnimal ModelArizonaBasal cell carcinomaBasic ScienceBioinformaticsBiological MarkersCarcinoma in SituChemopreventionChemopreventive AgentClinicalCoupledDangerousnessDevelopmentDrug TargetingEpithelialExperimental ModelsGenomicsGoalsHealthHealth Care CostsHistologicHumanIncidenceIndividualIntraepithelial NeoplasiaKnowledgeLaboratoriesLesionLightMalignant NeoplasmsMedicalModelingMolecular TargetMorbidity - disease rateMusNeoadjuvant TherapyNeoplasmsOperative Surgical ProceduresPathway AnalysisPathway interactionsPersonsPharmaceutical PreparationsPharmacologyPhase I Clinical TrialsPreclinical TestingPreventionPrevention ResearchPrevention approachPrevention strategyPreventiveProgram Research Project GrantsProteinsProteomicsRecurrenceResearchRiskRoleSafetySignal PathwaySignal TransductionSkinSkin CancerSkin CarcinogenesisSkin CarcinomaSquamous cell carcinomaSystems BiologyTLR4 geneTestingTissue SampleTopical applicationTranslational ResearchUV inducedUniversitiesbasecancer therapyclinical practicecostdesigndisorder riskdrug candidatedrug developmenthigh riskhuman subjecthuman tissuein vivoinnovationinterestmolecular targeted therapiesmortalitymouse modelmultidisciplinarynew technologynovelnovel therapeuticsphase 1 studypre-clinicalprecision medicinepreclinical studypremalignantpreventpreventive interventionprogramsreflectance confocal microscopyskin cancer preventionskin damageskin squamous cell carcinomasmall molecule inhibitorsolar ultraviolet radiationsun damagetertiary preventiontranscriptometranslational cancer researchtranslational research program
项目摘要
ABSTRACT
Overall Targeted Prevention of Non-Melanoma Skin Cancer
Skin cancer is the most common malignancy worldwide. One out of three new cancers is a skin cancer.
Approximately 5 million cases of non-melanoma skin cancer (NMSC) – basal cell carcinoma (BCC) and
cutaneous squamous cell carcinomas (cSCC) occur annually. Incidence rates for NMSC continue to rise,
creating a substantial impact on morbidity and health care costs that account for $8.1 billion/year for skin cancer
treatment. The majority of these lesions represent keratinocytic neoplasms. The overall goal of this multi-
institutional Program Project Grant (PPG) is to employ novel technologies and develop new targeted prevention
strategies to eradicate intraepithelial neoplasias in the skin (e.g. actinic keratosis, squamous cell carcinoma in
situ), and thereby, to dramatically reduce the risk of cSCC. To achieve this goal, we will conduct a multilevel
program of rational drug development, including: 1) to assess, in experimental models and human studies, the
significance of TLR4 and TOPK/PRPK signaling pathways in skin carcinogenesis leading to cSCC development;
2) to evaluate the relationship between TLR4 and TOPK/PRPK activation and previously established signaling
pathways of relevance in AK and cSCC development; 3) to identify and develop novel therapeutic preventive
agents that specifically “hit” these molecular targets in cSCC mouse models and effectively modulate their
signaling pathways; 4) to test the most promising target-specific agents in preclinical pharmacology models; and
5) to assess target engagement and safety of selected agents through pilot and Phase 1 clinical trials.
Knowledge of the key molecular targets in solar ultraviolet (UV) radiation signaling pathways and the
development of multiple topically administered agents that can hit and effectively modulate these targets
ultimately will allow for precision medicine based approaches in cSCC prevention. While the two basic science
projects (Projects 1 and 2) aim to identify and validate UV-induced signaling pathways and agents that modulate
these targets, the clinical project (Project 3) will undertake the task of moving leading candidate drugs from
mouse models into acute solar simulated light studies and Phase 1 clinical trials. Novel technologies include
signaling network analysis using state-of-the-art proteomic arrays and whole transcriptome analysis coupled with
the latest exploratory and downstream bioinformatic approaches and in vivo reflectance confocal microscopy for
non-invasive assessment and selection of tissue samples in human skin. This highly integrated and translational
research based program project, emphasizing a multidisciplinary, precision medicine approach for the prevention
of cSCC of the skin can also serve as a model for preventing other epithelial malignancies.
摘要
项目成果
期刊论文数量(0)
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会议论文数量(0)
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Clara Curiel-Lewandrowski其他文献
Clara Curiel-Lewandrowski的其他文献
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{{ truncateString('Clara Curiel-Lewandrowski', 18)}}的其他基金
Project 3: Translational Studies and Clinical Pharmacology of TLR4 and TOPK Inhibitors for Prevention of Squamous Cell Carcinoma of the Skin
项目3:TLR4和TOPK抑制剂预防皮肤鳞状细胞癌的转化研究和临床药理学
- 批准号:
10410014 - 财政年份:2019
- 资助金额:
$ 23.45万 - 项目类别:
Targeted Prevention for Non-Melanoma Skin Cancer
非黑色素瘤皮肤癌的针对性预防
- 批准号:
10015212 - 财政年份:2019
- 资助金额:
$ 23.45万 - 项目类别:
Project 3: Translational Studies and Clinical Pharmacology of TLR4 and TOPK Signaling Pathway Inhibitors for Prevention of Squamous Cell Carcinoma of the Skin
项目3:TLR4和TOPK信号通路抑制剂预防皮肤鳞状细胞癌的转化研究和临床药理学
- 批准号:
10252871 - 财政年份:2019
- 资助金额:
$ 23.45万 - 项目类别:
Project 3: Translational Studies and Clinical Pharmacology of TLR4 and TOPK Signaling Pathway Inhibitors for Prevention of Squamous Cell Carcinoma of the Skin
项目3:TLR4和TOPK信号通路抑制剂预防皮肤鳞状细胞癌的转化研究和临床药理学
- 批准号:
10475143 - 财政年份:2019
- 资助金额:
$ 23.45万 - 项目类别:
Project 3: Translational Studies and Clinical Pharmacology of TLR4 and TOPK Signaling Pathway Inhibitors for Prevention of Squamous Cell Carcinoma of the Skin
项目3:TLR4和TOPK信号通路抑制剂预防皮肤鳞状细胞癌的转化研究和临床药理学
- 批准号:
10015218 - 财政年份:2019
- 资助金额:
$ 23.45万 - 项目类别:
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