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: 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
• 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

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，在德克萨斯州尤为普遍。与声明的SPORE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，HIF -2α是肾细胞癌（ccRCC）的主要驱动因素；（ii）开发高度特异性的HIF-2转录因子的一流抑制剂，传统上被认为是“不可药物”的；（iii） ccRCC中BAP1基因突变的鉴定；（iv）建立散发性ccRCC的第一个分子遗传分类；（五）发现一种新的家族性肾癌综合征；（vi）新型无创肿瘤代谢成像工具的开发；（vii）在Wilms肿瘤中发现DROSHA突变。这些和其他令人兴奋的发现是肾癌项目（KCP; http://www.utsouthwestern.edu/research/kidney-cancer/index.html）的基础，该项目涉及70多名悉尼大学教师。本项目包含四个项目：项目一：靶向HIF-2治疗透明细胞肾细胞癌；项目二：评估功能及临床意义