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

基本信息

批准号：
9752982
负责人：
James Brugarolas
金额：
$ 213.8万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
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/9752982
关键词：
Achievement Adult Advocate Animal Model Area BAP1 gene Basic Science Bioavailable Biochemical Genetics Biological Markers Biotechnology Carcinoma Caring Child Childhood Classification Clear cell renal cell carcinoma Clinic Clinical Collaborations Communities Computerized Medical Record Coupled Data Data Analytics Dependence Development Diagnosis Dictionary Disease Early Diagnosis Enzymes Evaluation Experimental Genetics Faculty Family Foundations Genes Genomics Goals Home environment Human Image Imaging Device Immunotherapy Infrastructure Institution Internet Knowledge Laboratory Scientists Lead Link Magnetic Resonance Imaging Malignant Neoplasms Mediating Medical center Metabolic Metabolism Metastatic Carcinoma MicroRNAs Modeling Molecular Genetics Molecular Structure Mus Mutate Mutation Nephroblastoma Operative Surgical Procedures Oral Outcome Pathology Patient-Focused Outcomes Patients Pharmaceutical Preparations Phase I Clinical Trials Physicians Prevention Protein Isoforms Proteins Protocols documentation RNASE3L gene Radiation Oncology Renal Cell Carcinoma Renal Mass Renal carcinoma Research Research Personnel Resources Sampling Scientist Seminal Ships Specimen Structural Protein Syndrome TSC1 gene Talents Technology Texas Therapeutic Time Translational Research Translations Tumor Suppressor Genes Universities Update Work Xenograft procedure anticancer research base biobank career clinically actionable clinically significant diagnosis standard drug development experience first-in-human gene discovery genome editing high throughput screening improved indexing inhibitor/antagonist innovation investigator-initiated translational research kidney cell member metabolic abnormality assessment minimally invasive mouse model multidisciplinary nanoparticle new therapeutic target novel novel therapeutic intervention outcome prediction preservation prognostic significance programs protein structure public health relevance resistance mechanism surveillance study technological innovation tool transcription factor translational cancer research tumor tumor metabolism web-based tool

项目摘要

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，与既定的 SPORE 目的一致，我们的目标是开发一个繁荣的基础设施来支持“现状”。 -由最先进的研究者发起的转化研究，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)，我们相信杰出的基础科学奠定了基础UTSW 的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 -2α 的基因，这是肾细胞肾细胞癌 (ccRCC) 的主要驱动因素；高度特异性的一流 HIF-2 转录因子抑制剂，传统上被认为是“不可成药的”；(iii) 鉴定 ccRCC 中 BAP1 基因的突变；(iv) 建立第一个分子遗传学分类；散发性 ccRCC；(v) 一种新型家族性肾癌综合征的发现；(vi) 开发用于患者肿瘤代谢成像的新型非侵入性工具；以及 (vii) 在肾母细胞瘤中发现 DROSHA 突变。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，该计划涉及 70 多名 UTSW 教员。该 SPORE 包含 4 名教师。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；新型肿瘤抑制基因 BAP1；项目 3：来自肾癌细胞代谢和成像的临床可操作生物标志物；以及项目 4：DROSHA 突变在肾母细胞瘤中的预后意义和治疗潜力。核心：核心 B - 一个创新的“生物样本和病理学资源核心”，带有实时生物库核心 C - 一个“数据分析核心”，支持将样本链接到临床信息并集成的开创性网络工具；基因组学；核心 D——围绕研究肾癌而开发的工具构建的杰出“转化成像核心”，以 UTSW 的广泛肾癌研究为基础，以 19 个肾癌 LOI 为例进行说明。我们的患者倡导者计划由提交的六名患者倡导者组成，其中包括经验丰富的倡导者以及我们肾癌社区的成员。概述的项目说明了如何使用细胞、分子、结构、生化和遗传学进行严格的基础研究。实验方法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才华横溢的基础科学家、医生科学家和暴民的多学科努力，协同利用了我们在肾癌领域开发的优势和资源。肾癌计划旨在推进肾癌转化研究，最终目标是改善肾癌患者的治疗结果。