Dana-Farber/Harvard SPORE in Breast Cancer

描述(由申请人提供)： 这项申请是为2000年10月1日资助的Dana-Farber/哈佛大学乳腺癌分生孢子的第一次续展。该孢子是达纳-法伯/哈佛综合癌症中心(DF/HCC)乳腺癌计划的组成部分，包括来自所有主要DF/HCC站点、哈佛大学和麻省理工学院的研究人员。提出了六个项目：项目1寻找基底细胞样癌和BRCA1相关肿瘤共有的共同分子通路，并提出了一项针对HER2和ER阴性癌症的术前临床试验。项目2将通过寻找与曲妥珠单抗联合使用的新靶点和新药来改进HER2阳性癌症的治疗。项目3检查了ER阳性癌症对芳香酶抑制剂的反应，重点是共激活因子的作用和ER靶序列的受体占有率。项目4使用基因组方法研究人类原发和转移性疾病，解决了转移的难题。项目5考察了肿瘤-间质相互作用在早期乳腺肿瘤中的作用，并寻找在这种相互作用中活跃的诊断和治疗靶点。项目6将结合细胞和组织的功能研究和基于群体的研究，寻找与风险增加相关的激酶基因的等位基因。这些项目将得到以下核心资源的支持：组织和病理学，提供一系列组织和服务；临床研究，管理研究和患者之间的接口(招募、同意和注册)；队列研究，管理和维护研究和临床资源数据库；生物统计学，为孢子研究人员提供统计咨询；以及生物信息学，管理大型基因组数据集，并为寻求分析帮助的研究人员提供初步咨询。哈佛大学孢子学院将把其直接研究费用的13%用于职业发展和发展项目，并提出遴选和评估程序。沟通、规划和管理核心将通过评估、规划和修改我们的研究来不断改进孢子，以最大限度地提高我们对乳腺癌的影响。

DESCRIPTION (provided by applicant): This application is for the first renewal of the Dana-Farber/Harvard SPORE in Breast Cancer, funded October 1, 2000. This SPORE is a component of the Breast Cancer Program in the Dana-Farber/Harvard Comprehensive Cancer Center (DF/HCC), and includes investigators from all major DF/HCC sites, Harvard University and MIT. Six Projects are proposed: Project 1 seeks common molecular pathways shared by basal-like and BRCA1 -linked cancers, and proposes a preoperative clinical trial in HER2-and ER-negative cancers. Project 2 will improve the treatment of HER2-positive cancer by searching for new targets and new drugs to use in combination with trastuzumab. Project 3 examines the response of ER-positive cancers to aromatase inhibitors, focusing on the role of coactivators and receptor occupancy of ER target sequences. Project 4 addresses the conundrum of metastasis using genomic approaches to study human primary and metastatic disease. Project 5 examines the role of tumor - stromal interactions in the early breast neoplasia, and seeks diagnostic and therapeutic targets that are active in this interaction. Project 6 will combine functional studies in cells and tissues with population-based research to seek alleles of kinase genes associated with increased risk. These Projects will be supported by the following Core Resources: Tissue and Pathology, providing a range of tissues and services; Clinical Studies, managing the interface between research and patients (recruitment, consent, and registration); Cohort Studies, managing and maintaining databases of research and clinical resources; Biostatistics, providing statistical consultation to SPORE investigators; and Bioinformatics to manage large genomic data sets and provide initial consultation to investigators seeking analytical help. The Harvard SPORE will devote 13% of its direct research costs to Career Development and Developmental Projects, and proposes selection and evaluation processes. The Communication, Planning and Administration Core will continually improve the SPORE by evaluating, planning and modifying our research to maximize our impact on breast cancer.