Genetic and Signaling Pathways in Epithelial Thyroid Cancer
上皮性甲状腺癌的遗传和信号通路
基本信息
- 批准号:8657014
- 负责人:
- 金额:$ 217.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-03-01 至 2018-03-31
- 项目状态:已结题
- 来源:
- 关键词:12q144q328q24AddressAreaBRAF geneBehaviorBiological AssayCancer FamilyCancer ModelCandidate Disease GeneCellsClinicalClinical TrialsDataDevelopmentDiagnosisDiseaseDisease ProgressionEarly DiagnosisEnhancersEpithelialEventFamilyFollicular thyroid carcinomaGenesGeneticGenetic ModelsGenomicsGoalsImaging TechniquesIn VitroIncidenceIndividualIndolentIodineMEKsMalignant NeoplasmsMalignant neoplasm of thyroidMediatingMethodsMitochondriaModelingMolecular GeneticsMolecular TargetMusNeoplasm MetastasisNeoplasmsOncogenesOutcomePTEN genePapillary thyroid carcinomaPathogenesisPathway interactionsPatientsPlayPopulationPredispositionPrimary NeoplasmProcessRegulationResearchResistanceRiskRisk AssessmentRoleSignal PathwaySignal TransductionSusceptibility GeneTestingTherapeuticThyroid GlandTissuesToxic effectTranslatingUnited StatesVariantWomanWorkbasecancer cellcancer geneticscancer riskcell motilityclinical careclinical practicedesigneffective therapygenetic linkage analysisgenetic variantimprovedin vivoinhibitor/antagonistkinase inhibitorkindredmembermenmodel designmouse modelnew technologynew therapeutic targetnovelp21 activated kinasepositional cloningsmall moleculetumortumor progressiontumorigenesisuptake
项目摘要
DESCRIPTION (provided by applicant): The primary goal of this P01 is to improve the outcomes and lives of patients with thyroid cancer by identifying genetically "at-risk" individuals
allowing for early diagnosis and prediction of tumor behavior, new pathways that influence cancer development and progression, and improving outcomes of patients with metastatic disease by improving existing therapies or validating new treatment targets. Several factors support the importance of applying these efforts to thyroid cancer: (1) Thyroid cancer incidence is rising at the fastest rate of all malignancies in the United States. (2) Thyroid cancer typicall takes an indolent course when patients are diagnosed early, thus with the increasing incidence there is an ever enlarging population of individuals surviving long-term. (3) For patients with more aggressive forms of thyroid cancer, current treatment options need to be improved or replaced with more effective treatments. Over the course of the first cycle of this P01 our group has together worked toward these goals and made key observations with potential to impact on patients with differentiated thyroid cancer (papillary and follicular). The goal for this competing
renewal is to extend the work on the most promising findings that have greatest likelihood to be translated into practice or that represent key advances in the field with potential to alter paradigms used in research or clinical practice. Specifically, we will functionally characterize genes that predispose to PTC in families identified in the first cycle of the P01 and apply new technologies to a larger number of informative families to identify more potential genes that predispose to PTC (Project 1), extend the work using a candidate gene approach for FTC and PTC risk that has identified interactions between signaling pathways (Project 2); design approaches to enhance 1-131 therapy using novel mouse imaging techniques developed in the P01 and extend that work to identify other unknown regulators of this process (Project 3); and fully determine the role and potential therapeutic importance of p21 activated kinase (PAK), a newly identified signaling pathway downstream of BRAF, in thyroid cancer in vivo, and determine its role in resistance to RAF inhibitors (Project 4).
描述(由申请人提供):本P01的主要目标是通过识别遗传“高危”个体来改善甲状腺癌患者的结局和生活
允许早期诊断和预测肿瘤行为、影响癌症发展和进展的新途径,以及通过改善现有疗法或验证新的治疗靶点来改善患有转移性疾病的患者的结果。有几个因素支持将这些努力应用于甲状腺癌的重要性:(1)甲状腺癌的发病率在美国所有恶性肿瘤中上升最快。(2)当患者被早期诊断时,甲状腺癌通常采取惰性过程,因此随着发病率的增加,长期存活的个体人口不断增加。(3)对于患有更具侵袭性形式的甲状腺癌的患者,需要改进目前的治疗方案或用更有效的治疗方法取代。在P01的第一个周期中,我们的团队共同努力实现这些目标,并进行了可能影响分化型甲状腺癌(乳头状和滤泡状)患者的关键观察。这次比赛的目标是
更新是为了扩大最有希望的研究结果的工作,这些研究结果最有可能转化为实践,或者代表了该领域的关键进展,有可能改变研究或临床实践中使用的范式。具体而言,我们将在P01的第一个周期中鉴定的家族中对PTC易感基因进行功能表征,并将新技术应用于大量信息丰富的家族,以鉴定更多潜在的PTC易感基因(项目1),使用候选基因方法扩展FTC和PTC风险的工作,该方法已确定信号通路之间的相互作用(项目2);设计方法,使用P01中开发的新型小鼠成像技术增强1-131治疗,并将该工作扩展到识别该过程的其他未知调节剂(项目3);并充分确定p21激活激酶(PAK)的作用和潜在的治疗重要性,PAK是一种新鉴定的BRAF下游信号通路,在甲状腺癌体内,并确定其在抵抗RAF抑制剂的作用(项目4)。
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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{{ truncateString('Matthew D Ringel', 18)}}的其他基金
RCAN 1.4 metastasis suppressor in thyroid cancer
RCAN 1.4 甲状腺癌转移抑制因子
- 批准号:
9973560 - 财政年份:2020
- 资助金额:
$ 217.65万 - 项目类别:
RCAN 1.4 metastasis suppressor in thyroid cancer
RCAN 1.4 甲状腺癌转移抑制因子
- 批准号:
10604328 - 财政年份:2020
- 资助金额:
$ 217.65万 - 项目类别:
RCAN 1.4 metastasis suppressor in thyroid cancer
RCAN 1.4 甲状腺癌转移抑制因子
- 批准号:
10400004 - 财政年份:2020
- 资助金额:
$ 217.65万 - 项目类别:
Role of p21-activated kinases in thyroid cancer
p21 激活激酶在甲状腺癌中的作用
- 批准号:
10377551 - 财政年份:2018
- 资助金额:
$ 217.65万 - 项目类别:
The OSU Center for Clinical and Translational Science: Advancing Today's Discoveries to Improve Health
俄勒冈州立大学临床和转化科学中心:推进当今的发现以改善健康
- 批准号:
10414809 - 财政年份:2018
- 资助金额:
$ 217.65万 - 项目类别:
The Ohio State University and MD Anderson Cancer Center Thyroid Cancer SPORE
俄亥俄州立大学和 MD 安德森癌症中心甲状腺癌孢子
- 批准号:
8741949 - 财政年份:2013
- 资助金额:
$ 217.65万 - 项目类别:
Developing Combination Therapies for Medullary Thyroid Cancer
开发甲状腺髓样癌的联合疗法
- 批准号:
8588547 - 财政年份:2013
- 资助金额:
$ 217.65万 - 项目类别:
The Ohio State University and MD Anderson Cancer Center Thyroid Cancer SPORE
俄亥俄州立大学和 MD 安德森癌症中心甲状腺癌孢子
- 批准号:
8548721 - 财政年份:2013
- 资助金额:
$ 217.65万 - 项目类别:
Integrated Clinicopathology and Biorespository Core
综合临床病理学和生物仓库核心
- 批准号:
8588551 - 财政年份:2013
- 资助金额:
$ 217.65万 - 项目类别:
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