Clinico-Genomics for Improved Ovarian Cancer Treatment

改善卵巢癌治疗的临床基因组学

• 批准号: 6852260
• 负责人: JENNIFER L. CLARKE
• 金额: $ 13.07万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6852260
• 关键词: angiogenesis inhibitors; biotechnology; clinical research; combination cancer therapy; drug resistance; gene expression profiling; gene therapy; genetic polymorphism; genetic susceptibility; human data; human genetic material tag; microarray technology; neoplasm /cancer chemotherapy; neoplasm /cancer epidemiology; neoplasm /cancer genetics; neoplasm /cancer radioimmunotherapy; neoplasm /cancer relapse /recurrence; neoplasm /cancer therapy; outcomes research; ovary neoplasms; platinum; prognosis; therapy design /development; tissue resource /registry; women' s health

DESCRIPTION (provided by applicant): My primary objective is the development of a knowledge base in cancer genomics and oncology that will complement my knowledge in statistics and enables me to identify and apply my statistical skills and abilities in promising areas of breast and ovarian cancer genomics through my position as Senior Scientist in the Computational and Applied Genomics Program (CAGP) in the Institute for Genome Studies and Policy (IGSP) at Duke University. My proposed program involves formal coursework in cancer biology, genetics, and epidemiology tailored to the specific loci of this grant and the context of oncogenesis. I will apply my knowledge in molecular oncology through participation in the lab of my mentor, Joe Nevins, Ph.D., Director of the Center for Genome Technology in IGSP. Andrew Berchuck, M.D., gynecological oncologist in the Duke Comprehensive Cancer Center, will serve as my co-mentor and will direct my education in the clinical application of my knowledge within the context of ovarian cancer. My education in cancer epidemiology will progress through coursework and research in genetic epidemiology under the co-mentorship of Joellen Schildkraut, Ph.D., Director of the Epidemiology Division of the Program in Cancer Prevention, Detection, and Control and Associate Professor in the Department of Community and Family Medicine in the Duke Comprehensive Cancer Center. The goals of my research plan take advantage of recent developments in the use of genome-scale measures of gene expression and advanced computational tools to identify patterns of gene expression that are associated with or predict various characteristics and outcomes in ovarian cancers. My research is designed to aid in the identification of strategies for developing new therapeutic targets for the treatment of patients with advanced-stage epithelial ovarian cancer who do not respond to platinum/taxane-based adjuvant therapy and may or may not respond to salvage chemotherapy. I believe the importance of this work lies in the fact that chemosensitivity is the major determinant of outcome for advanced stage epithelial ovarian cancer, and the ability to predict outcomes such as chemo-responsiveness will be a powerful tool in disease treatment. A cooperative goal is to determine whether distinct subsets of ovarian cancer can be better defined by simultaneous consideration of etiologic and inherited risk factors and molecular features as expressed in gene expression data. This strategy represents a new approach in seeking to delineate the molecular epidemiology of ovarian cancer and may identify gene polymorphisms which influence relative risk of disease and clinical outcome. The potential results represent a useful tool in determining the most appropriate treatment protocol for each patient. The proposed development program has been designed to provide me with a background in cancer genomics and epidemiology which will enable me to focus the interdisciplinary nature of the CAGP environment on cancer genomic research collaborations between geneticists, breast and ovarian oncologists, statisticians, and epidemiologists.

描述（由申请人提供）：我的主要目标是开发癌症基因组学和肿瘤学知识库，这将补充我在统计学方面的知识，并使我能够在乳腺癌和卵巢癌基因组学的有前途的领域识别和应用我的统计技能和能力我是杜克大学基因组研究与政策研究所 (IGSP) 计算和应用基因组学项目 (CAGP) 的高级科学家。我提议的项目涉及癌症生物学、遗传学和流行病学的正式课程，这些课程是根据这笔资助的特定位点和肿瘤发生的背景量身定制的。我将通过参与我的导师、IGSP 基因组技术中心主任 Joe Nevins 博士的实验室，应用我在分子肿瘤学方面的知识。杜克大学综合癌症中心的妇科肿瘤学家 Andrew Berchuck 医学博士将担任我的共同导师，并将指导我将我的知识应用于卵巢癌的临床应用。我在癌症流行病学方面的教育将在癌症预防、检测和控制项目流行病学部主任兼系副教授 Joellen Schildkraut 博士的共同指导下，通过遗传流行病学的课程和研究取得进展杜克综合癌症中心社区和家庭医学博士。 我的研究计划的目标是利用基因表达的基因组规模测量和先进计算工具的最新进展来识别与卵巢癌的各种特征和结果相关或预测的基因表达模式。我的研究旨在帮助确定开发新治疗靶点的策略，用于治疗晚期上皮性卵巢癌患者，这些患者对铂类/紫杉烷类辅助治疗没有反应，并且可能对挽救性化疗有反应，也可能没有反应。我相信这项工作的重要性在于，化疗敏感性是晚期上皮性卵巢癌结果的主要决定因素，而预测化疗反应等结果的能力将成为疾病治疗的强大工具。合作目标是确定是否可以通过同时考虑病因和遗传风险因素以及基因表达数据中表达的分子特征来更好地定义卵巢癌的不同亚型。该策略代表了一种描述卵巢癌分子流行病学的新方法，并可能识别影响疾病相对风险和临床结果的基因多态性。潜在的结果代表了为每位患者确定最合适的治疗方案的有用工具。 拟议的开发计划旨在为我提供癌症基因组学和流行病学的背景，这将使我能够将 CAGP 环境的跨学科性质集中在遗传学家、乳腺癌和卵巢肿瘤学家、统计学家和流行病学家之间的癌症基因组研究合作上。