Enhancing Translational Science via Prospective Investigation

通过前瞻性调查加强转化科学

基本信息

批准号：
9102996
负责人：
WENDY KIMRYN RATHMELL
金额：
$ 16.29万
依托单位：
VANDERBILT UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2018-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9102996
关键词：
Atlases Attention Basic Science Behavior Biological Biological Markers Biology Cancer Biology Career Choice Caring Cessation of life Characteristics Classification Clear Cell Clinical Clinical Data Clinical Research Clinical Sciences Clinical Trials Complex Dasatinib Data Data Collection Data Set Development Diagnostic Disease Doctor of Philosophy Education Evaluation Event Face Faculty Fellowship Functional Imaging Gene Expression Generations Genetic Genetic Markers Genome Genomics Health Human Hypoxia Inducible Factor Incidence Investigation Kidney Kidney Neoplasms Knowledge Light Lymphoma Malignant Neoplasms Medical Oncology Mentors Metabolic Methods MicroRNAs Modeling Molecular Genetics Molecular Models Molecular Profiling Motivation Mutation Neoadjuvant Therapy Nephrectomy Nursing Faculty Orphan Output Palliative Care Pathway interactions Patient Care Patient-Focused Outcomes Patients Pattern Perfusion Phosphotransferases Physicians Positron-Emission Tomography Preparation Prognostic Marker Property Radiation Oncology Radiology Specialty Recurrence Refractory Regulation Renal Cell Carcinoma Renal carcinoma Research Research Activity Research Personnel Research Project Grants Resources Risk Assessment Risk Reduction Role Sampling Scientist Series Services Shapes Signal Pathway Signal Transduction Staging Students Therapeutic Time Translational Research Tumor Burden Urologic Oncology VHL mutation Validation Vascular Endothelial Growth Factors Work bench to bedside biological systems cancer type career chemotherapy clinical decision-making clinically actionable clinically relevant design disorder risk disorder subtype drug development effective therapy fascinate fundamental research graduate student hypoxia inducible factor 1 improved innovation insight interest mRNA Expression member molecular marker molecular modeling mouse model multidisciplinary neoplastic cell novel novel strategies outcome forecast patient oriented patient oriented research patient stratification predictive marker programs prospective research clinical testing response role model targeted treatment therapeutic development therapy development therapy outcome tumor tumor heterogeneity tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Renal cell carcinoma is a cancer with major unmet clinical needs for which the incidence is steadily rising, and which is increasingly becoming a multidisciplinary disease. Our understanding of the underlying genetic and molecular factors which shape the clinical outcomes for patients with this cancer has advanced to a stage where application to clinical decision-making is imperative. An enhanced understanding of the molecular and genetic events which contribute to disease recurrence and death would significantly improve our ability to stratify patients into clinically relevant classes, devise strategies to achieve risk reduction and identify novel methods to treat patients with this cancer. We have previously identified several important biological features of these cancers through our translational efforts, which are instructional in discriminating the pathways to cancer in the kidney. I propose to extend these features as biomarkers in four projects in various stages of development as vehicles to introduce junior members of our clinical team to the unique potential of prospective investigation. In brief, the four projects are: 1) Prospective biomarker assessment and longitudinal clinical data collection for prognostic biomarker validation. 2) Evaluation of clinical benefit to neoadjuvant treatment with pazopanib prior to nephrectomy, with prospective development of response - predictive biomarkers. 3) Elucidation of the functional relationship of genomic intratumoral heterogeneity with tumor perfusion and metabolic properties using MR-PET. 4) Evaluation of a kinase biomarker expression profile to stratify patients for response to dasatinib. This proposal will provide a series of optimal clinically annotated datasets for developing biological and pharmacological relationships as well as serving as a platform for developing a multidisciplinary cadre of established investigators through the involvement of junior faculty and fellow mentoring relationships. In addition to providing ground-level support fo this endeavor, the support of this proposal will allow me to have the protected time and a platform from which to continue and expand my current patient-oriented research efforts as well as the mentoring efforts of junior faculty, fellows and residents, as well as post-graduate students, focusing on MD-PhD student preparation for the physician- scientist career path. This work will provide key insights to enable drug development, more accurate disease risk assessment, suggest possible therapeutic strategies, and model the biology of common molecular and genetic changes responsible for renal oncogenesis while continuing to build a robust multidisciplinary team. Further, these studies are ideally suited for developing the careers of junior faculty and clinical trainees, and will serve as the launching point for studies to be implemented by my mentees.

描述（由申请人提供）：肾细胞癌是一种临床需求未得到满足的癌症，其发病率正在稳步上升，并且日益成为一种多学科疾病。我们对影响这种癌症患者临床结果的潜在遗传和分子因素的理解已经发展到必须应用于临床决策的阶段。加深对导致疾病复发和死亡的分子和遗传事件的了解，将显着提高我们将患者分为临床相关类别、制定降低风险的策略以及确定治疗这种癌症患者的新方法的能力。我们之前已经通过翻译工作确定了这些癌症的几个重要生物学特征，这对于区分肾脏癌症的途径具有指导意义。我建议将这些特征作为生物标志物扩展到处于不同开发阶段的四个项目中，作为向我们临床团队的初级成员介绍前瞻性研究的独特潜力的工具。简而言之，这四个项目是：1）用于预后生物标志物验证的前瞻性生物标志物评估和纵向临床数据收集。 2) 评估肾切除术前帕唑帕尼新辅助治疗的临床益处，并前瞻性开发反应预测生物标志物。 3) 使用 MR-PET 阐明肿瘤内基因组异质性与肿瘤灌注和代谢特性的功能关系。 4) 评估激酶生物标志物表达谱，以对患者对达沙替尼的反应进行分层。该提案将提供一系列最佳的临床注释数据集，用于发展生物学和药理学关系，并作为一个平台，通过初级教师和同事指导关系的参与，培养已建立的研究人员的多学科骨干队伍。除了为这项工作提供基础支持外，该提案的支持将使我拥有受保护的时间和平台，以继续和扩大我目前以患者为导向的研究工作以及初级教师的指导工作、研究员和住院医生以及研究生，重点关注医学博士-博士生为医师科学家职业道路做准备。这项工作将为药物开发、更准确的疾病风险评估、提出可能的治疗策略以及对肾肿瘤发生的常见分子和遗传变化的生物学建模提供关键见解，同时继续建立一个强大的多学科团队。此外，这些研究非常适合发展职业生涯初级教师和临床实习生，并将作为我的学员实施研究的起点。