The University of Texas Southwestern Medical Center SPORE in Kidney Cancer

德克萨斯大学西南医学中心 SPORE 在肾癌中的应用

• 批准号: 9071063
• 负责人: James Brugarolas
• 金额: $ 216.2万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9071063
• 关键词: Achievement; Adult; Advocate; Animal Model; Area; BAP1 gene; Basic Science; Bioavailable; Biochemical Genetics; Biological Markers; Biotechnology; Cancer Patient; Caring; Cells; Child; Childhood; Classification; Clear Cell; Clinic; Clinical; Collaborations; Communities; Computerized Medical Record; Coupled; Data; Data Analytics; Dependency; Development; Diagnosis; Dictionary; Disease; Early Diagnosis; Enzymes; Evaluation; Faculty; Family; Foundations; Genes; Genomics; Goals; Health; Home environment; Human; Image; Imaging Device; Immunotherapy; Institution; Internet; Knowledge; Laboratory Scientists; Lead; Life; Link; Magnetic Resonance Imaging; Malignant Neoplasms; Mediating; Medical center; Metabolic; Metabolism; MicroRNAs; Modeling; Molecular; Molecular Genetics; Mus; Mutate; Mutation; Nephroblastoma; Nuclear Hormone Receptors; Online Systems; Operative Surgical Procedures; Outcome; Pathology; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Phase I Clinical Trials; Physicians; Prevention; Process; Protein Isoforms; Proteins; Protocols documentation; RNASE3L gene; Radiation Oncology; Renal Cell Carcinoma; Renal Mass; Renal carcinoma; Research; Research Infrastructure; Research Personnel; Resources; Sampling; Scientist; Seminal; Shipping; Ships; Specimen; Syndrome; TSC1 gene; Technology; Texas; Therapeutic; Time; Translational Research; Translations; Treatment outcome; Tumor Suppressor Genes; Universities; Update; Work; Xenograft procedure; anticancer research; base; biobank; career; clinically actionable; clinically significant; diagnosis standard; drug development; empowered; experience; gene discovery; genome editing; high throughput screening; imaging biomarker; improved; indexing; inhibitor/antagonist; innovation; investigator-initiated translational research; member; metabolic abnormality assessment; minimally invasive; mouse model; multidisciplinary; nanoparticle; novel; novel therapeutic intervention; prognostic significance; programs; protein structure; resistance mechanism; surveillance study; technological innovation; tool; transcription factor; tumor; tumor metabolism

DESCRIPTION (provided by applicant): Kidney cancer is one of the top ten most common cancers in the U.S. and is particularly prevalent in Texas. Consistent with the stated SPORE purpose, our objective is to develop a thriving infrastructure supporting "state-of-the-art investigator-initiated translational research that will contribute to improved prevention, early detection, diagnosis, and treatment" of kidney cancer (both adult and pediatric). At UT Southwestern Medical Center (UTSW), we believe that outstanding basic science sets the foundation for outstanding translation. UTSW investigators have made seminal discoveries in kidney cancer, including (i) the discovery of the gene encoding HIF -2α - the main driver of lear-cell renal cell carcinoma (ccRCC); (ii) the development of a highly specific first-in-class inhibitr of the HIF-2 transcription factor, traditionally considered "undruggable"; (iii) the identificationof mutations in the BAP1 gene in ccRCC; (iv) the establishment of the first molecular genetic classification of sporadic ccRCC; (v) the discovery of a novel familial kidney cancer syndrome; (vi) the development of novel non-invasive tools for imaging tumor metabolism in patients; and (vii) the discovery of DROSHA mutations in Wilms tumors. These and other exciting discoveries were the basis of a Kidney Cancer Program (KCP; http://www.utsouthwestern.edu/research/kidney-cancer/index.html) involving over 70 UTSW faculty. This SPORE contains four projects: Project 1: Targeting HIF-2 for the treatment of clear-cell renal cell carcinoma; Project 2: Evaluation of the functional and clinical significance of the novel tumor suppressor gene BAP1; Project 3: Clinically actionable biomarkers from renal cell carcinoma metabolism and imaging; and Project 4: Prognostic significance and therapeutic potential of DROSHA mutations in Wilms tumor. They are supported by an Administrative Core (Core A) and three other cores: Core B - an innovative "Biospecimen and Pathology Resources Core" with a live BioBank; Core C - a "Data Analytics Core" supporting a pioneering web-tool linking samples to clinical information and integrated genomics; and Core D - an outstanding "Translational Imaging Core" built around tools developed to study kidney cancer. A Developmental Research Program and a Career Enhancement Program thrive upon the wide scope of kidney cancer research at UTSW illustrated by the 19 LOIs with kidney-cancer relevant preliminary data submitted. Our Patient Advocate Program is comprised of six patient advocates including both experienced advocates as well as members of our kidney cancer community. The projects outlined illustrate how rigorous basic research using cellular, molecular, structural, biochemical, and genetic experimental approaches has increased our knowledge of kidney cancer, and is impacting the clinic. In summary, this Kidney Cancer SPORE represents a multidisciplinary effort from talented basic scientists, physician-scientists, and clinicians that synergistically leverages the strengths and resources we have developed in the Kidney Cancer Program to advance kidney cancer translational research, with the ultimate goal of improving kidney cancer patient outcomes.

描述（由申请人提供）：肾癌是美国十大最常见的癌症之一，在德克萨斯州尤其普遍。与SPORE的既定目标一致，我们的目标是开发一个蓬勃发展的基础设施，支持“最先进的制药商发起的转化研究，这将有助于改善肾癌（成人和儿童）的预防，早期检测，诊断和治疗”。在UT西南医学中心（UTSW），我们相信优秀的基础科学为优秀的翻译奠定了基础。UTSW研究人员在肾癌方面取得了开创性的发现，包括（i）发现了编码HIF-2 α的基因--lear-cell renal cell carcinoma（ccRCC）的主要驱动因素;（ii）开发了高度特异性的HIF-2转录因子，传统上被认为是“不可治疗的”;（iii）鉴定了ccRCC中BAP 1基因的突变;（iv）建立了散发性ccRCC的第一个分子遗传分类;（v）发现了一种新的家族性肾癌综合征;（vi）开发了用于成像患者肿瘤代谢的新型非侵入性工具;以及（vii）发现了Wilms肿瘤中的DROSHA突变。这些和其他令人兴奋的发现是肾癌计划（KCP; http：//www.utsouthwestern.edu/research/kidney-cancer/index.html）的基础，涉及70多名UTSW教师。该SPORE包含四个项目：项目1：靶向HIF-2治疗透明细胞肾细胞癌;项目2：评估HIF-2的功能和临床意义;项目3：评估HIF-2在肾透明细胞癌中的作用。 新的肿瘤抑制基因BAP 1;项目3：肾细胞癌代谢和成像的临床可行生物标志物;项目4：肾母细胞瘤中DROSHA突变的预后意义和治疗潜力。它们由一个管理核心（核心A）和其他三个核心支持：核心B -一个创新的“生物标本和病理学资源核心”，具有实时生物库;核心C -一个“数据分析核心”，支持一个将样本与临床信息和综合基因组学联系起来的开创性网络工具;核心D -一个杰出的“翻译成像核心”，围绕为研究肾癌而开发的工具。发展研究计划和职业提升计划在UTSW广泛的肾癌研究基础上蓬勃发展，19个LOI与肾癌相关的初步数据提交。我们的患者倡导者计划由六名患者倡导者组成，包括经验丰富的倡导者以及我们肾癌社区的成员。概述的项目说明了使用细胞，分子，结构，生物化学和遗传实验方法的严格基础研究如何增加了我们对肾癌的了解，并正在影响临床。总之，这个肾癌孢子代表了来自有才华的基础科学家，医生科学家和临床医生的多学科努力，协同利用我们在肾癌计划中开发的优势和资源来推进肾癌转化研究，最终目标是改善肾癌患者的预后。