Clinico-Genomics for Improved Ovarian Cancer Treatment

描述(申请人提供)：我的主要目标是建立一个癌症基因组学和肿瘤学的知识库，以补充我在统计学方面的知识，并使我能够通过我作为杜克大学基因组研究与政策研究所(IGSP)计算和应用基因组计划(CAGP)高级科学家的职位，在乳腺癌和卵巢癌基因组学有前途的领域识别并应用我的统计技能和能力。我建议的计划包括癌症生物学、遗传学和流行病学的正式课程，这些课程是根据这笔赠款的特定位置和肿瘤发生的背景而量身定做的。我将通过参加我的导师、IGSP基因组技术中心主任乔·内文斯博士的实验室，应用我在分子肿瘤学方面的知识。安德鲁·伯查克，医学博士，杜克综合癌症中心的妇科肿瘤学家，将作为我的共同导师，指导我在卵巢癌背景下临床应用我的知识的教育。我在癌症流行病学方面的教育将通过在乔伦·斯柴尔德博士的共同指导下进行遗传流行病学的课程学习和研究而取得进展。乔伦·斯柴尔德博士是杜克综合癌症中心癌症预防、检测和控制项目流行病学部主任，也是社区和家庭医学部的副教授。 我的研究计划的目标是利用基因组规模的基因表达测量和先进的计算工具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的最新发展。我的研究旨在帮助确定为晚期上皮性卵巢癌患者开发新的治疗靶点的策略，这些患者对以铂/紫杉烷为基础的辅助治疗无效，对挽救化疗可能有效也可能无效。我认为这项工作的重要性在于这样一个事实，即化疗敏感性是晚期上皮性卵巢癌预后的主要决定因素，预测预后的能力，如化疗反应，将成为疾病治疗的有力工具。一个合作的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确定卵巢癌的不同亚型。这一策略代表了一种新的方法，试图描绘卵巢癌的分子流行病学，并可能识别影响疾病相对风险和临床结果的基因多态。潜在的结果是为每个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方面的背景知识，使我能够将CAGP环境的跨学科性质集中在遗传学家、乳腺和卵巢肿瘤学家、统计学家和流行病学家之间的癌症基因组研究合作上。

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.