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（由适用提供）：肾癌是美国十大最常见的癌症之一，在德克萨斯州尤为普遍。与既定的孢子目的一致，我们的目标是开发一个蓬勃发展的基础设施，支持“最先进的研究者启动的转化研究，这将有助于改善肾癌（成人和儿科）的预防，早期发现，诊断和治疗”。在UT西南医学中心（UTSW），我们认为杰出的基础科学为杰出翻译奠定了基础。 UTSW研究人员在肾癌中发现了第二个发现，包括（i）编码HIF-2α的基因 - 学习细胞肾细胞癌的主要驱动力（CCRCC）； （ii）开发高度特定的HIF-2转录因子的一流抑制剂，传统上被认为是“不可能”的； （iii）CCRC中BAP1基因突变的鉴定； （iv）建立零星CCRC的第一个分子遗传分类； （v）发现一种新型的家庭肾癌综合征； （vi）开发了用于成像患者肿瘤代谢的新型非侵入性工具； （vii）在威尔姆斯肿瘤中发现了Drosha突变。这些和其他令人兴奋的发现是肾脏癌症计划（KCP; http://www.utsouthwestern.edu/research/kidney-cancer/index.html）的基础。该孢子包含四个项目：项目1：靶向HIF-2用于治疗透明细胞肾细胞癌；项目2：评估功能和临床意义的评估 新型肿瘤抑制基因BAP1；项目3：肾细胞癌代谢和成像的临床可行的生物标志物；和项目4：Wilms肿瘤中Drosha突变的预后意义和治疗潜力。它们得到了行政核心（核心A）和其他三个核心的支持：核心B-具有现场生物库的创新的“双记录和病理资源核心”；核心C-支持开拓性网络工具的“数据分析核心”，将样本与临床信息和集成基因组学联系起来；和核心D-围绕开发用于研究肾癌的工具而建立的出色的“转化成像核心”。一项发展研究计划和一项职业增强计划在UTSW的肾脏癌研究范围内壮成长，由19位LOIS插图，并提交了肾脏癌的相关初步数据。我们的患者拥护者计划完成了六名患者拥护者，包括经验丰富的拥护者以及我们的肾脏癌社区成员。这些项目概述了使用细胞，分子，结构，生化和遗传实验方法进行严格的基础研究，从而增加了我们对肾癌的了解，并且正在影响诊所。总而言之，这款肾癌孢子代表了才华横溢的基础科学家，身体科学家和临床医生的跨学科努力，该措施协同利用了我们在肾脏癌症计划中开发的优势和资源，以推动肾脏癌转化研究，并取得了改善肾脏癌症患者的最终目标。