Pharmacogenetics of Anticancer Agents Research Group

抗癌药物遗传学研究组

• 批准号: 7938267
• 负责人: MARK J RATAIN
• 金额: $ 6.09万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7938267
• 关键词: Pharmacogenetics; Anticancer; Agents; Research; Group

DESCRIPTION (provided by applicant): This proposal represents the scientific accomplishments, contributions to the NIH Pharmacogenetics Research Network (PGRN), and plans for our Pharmacogenetics of Anticancer Agents Research (PAAR) Group. The PAAR Group includes a multidisciplinary team of investigators from the University of Chicago (UC), St. Jude Children's Research Hospital (SJCRH), MD Anderson Cancer Center, and the University of Pittsburgh. The PAAR Group will continue to be chaired by Mark Ratain (UC), a medical oncologist, and vice-chaired by Mary Rolling (SJCRH), a molecular and clinical pharmacologist. The Group is governed by an Executive Committee of nine senior investigators. Our goal is to improve the efficacy of anticancer drugs by elucidating the impact and mechanisms of germ line polymorphisms affecting the pharmacokinetics and pharmacodynamics of anticancer agents. Our aims include: (1) To enhance pharmacogenetic knowledge and deposition in PharmGKB through (a) identification of new polymorphisms in drug metabolizing enzymes, transporters, or targets relevant to anticancer agents, (b) detailed analysis of the haplotypic structure and population diversity of important candidate genes, (c) determination of the association between newly discovered and previously identified polymorphisms and haplotypes (genotype) and variability in toxicity and/or response to anticancer agents (phenotype), and (d) collaboration and interaction with other PGRN investigators and the NCI-funded Cooperative Groups; (2) To create shared resources of value for other PGRN investigators and users of PharmGKB; and (3) To demonstrate the clinical utility of pharmacogenetic knowledge. Over the past funding period, the group has demonstrated substantial productivity as evidenced by > 54 publications and over 229 publicly-available PharmGKB deposits. Our scientific plans include a consistent phenotype-to-genotype approach and are organized around four Projects (childhood leukemia, colorectal cancer, CYP3A and related genes, cellular susceptibility), two Platforms (Whole Genome and Deep Re-sequencing), and five Cores (Administrative, Study Design and Data Analysis, Molecular Genetics, Liver Tissue, Cell Line). Our objective is to define how genetic variability impacts phenotypic variability in anticancer drug response, with the long-term aspiration that individualization of therapy, based on genomics, will improve efficacy and decrease adverse effects of anticancer agents.

描述（由申请人提供）：本提案代表了科学成就，对NIH药物遗传学研究网络（PGRN）的贡献，以及我们抗癌药物药物遗传学研究（PAAR）小组的计划。PAAR小组包括来自芝加哥大学（UC）、圣犹达儿童研究医院（SJCRH）、MD安德森癌症中心和匹兹堡大学的多学科研究小组。PAAR小组将继续由医学肿瘤学家Mark Ratain （UC）担任主席，由分子和临床药理学家Mary Rolling （SJCRH）担任副主席。小组由九名高级调查人员组成的执行委员会管理。我们的目标是通过阐明种系多态性对抗癌药物药代动力学和药效学的影响和机制来提高抗癌药物的疗效。我们的目标包括：(1)通过(a)鉴定与抗癌药物相关的药物代谢酶、转运体或靶点的新多态性，(b)详细分析重要候选基因的单倍型结构和群体多样性，增强药物遗传学知识和在PharmGKB中的沉积；(c)确定新发现和先前鉴定的多态性和单倍型（基因型）与毒性和/或对抗癌药物反应的变异性（表型）之间的关联，以及(d)与其他PGRN研究者和nci资助的合作小组的合作和互动；(2)为其他PGRN研究者和PharmGKB用户创造有价值的共享资源；(3)展示药物遗传学知识的临床应用。在过去的资助期间，该小组已经证明了巨大的生产力，bbbb54出版物和超过229个公开的PharmGKB存款证明了这一点。我们的科学计划包括一致的表型到基因型方法，并围绕四个项目（儿童白血病，结直肠癌，CYP3A及相关基因，细胞易感性），两个平台（全基因组和深度重测序）和五个核心（管理，研究设计和数据分析，分子遗传学，肝脏组织，细胞系）进行组织。我们的目标是确定遗传变异如何影响抗癌药物反应的表型变异，并长期期望基于基因组学的个体化治疗将提高疗效并减少抗癌药物的不良反应。