Seattle Cancer Consortium Breast SPORE

描述(由申请者提供)：由Peggy Porter博士和Martin“Mac”Cheever博士领导的西雅图癌症联盟(SCC)乳腺孢子申请将来自弗雷德·哈钦森癌症研究中心(FHCRC)和华盛顿大学(UW)的临床和实验室研究人员聚集在一起，旨在积极影响患有乳腺癌或有乳腺癌风险的女性的预防、检测、治疗和护理。为了实现这一目标，我们将在高度翻译的项目中进行战略研究，随着孢子的进展开发新的研究方向，并资助新的研究人员-那些开始他们的职业生涯的人，以及那些新成立的专注于乳腺癌的职业生涯的人。研究人员认为，乳腺癌对当前治疗方法的高度不同反应是该疾病的基因和表型异质性的一种表现。因此，关于孢子的最初项目将集中在这样的假设上，即靶向治疗需要集中在适当的肿瘤类型上。为西雅图孢子提出的四个主要研究项目对这个主题进行了扩展。其中两个项目是以临床试验和专注于床边到工作台的转换方法启动的。其中三个项目的重点是深入了解治疗的耐药性，并最终确定需要哪些靶向治疗来治疗耐药肿瘤。项目1将应用乳腺癌中p27kip1细胞周期调控的基本发现来预测死亡率和治疗反应。项目2将使用精致特异和工程化的中央记忆T细胞，通过疫苗和治疗来靶向异常表达的肿瘤相关蛋白。项目3将确定乳房成像代谢/血流灌注不匹配的生物学基础，该特征预测预后较差，对系统治疗的反应较差。项目4将利用一个具有良好特征的基于人群的队列来确定特定的DNA损伤途径生物标记物，这些生物标记物可以防止乳腺癌女性患者过度或不足的治疗。这四个项目加在一起，既提供了短期和长期的翻译回报，也提供了新发现的潜力，这些发现将影响乳腺癌护理的重要方面。孢子由发展研究计划(DRP)、职业发展计划(CDP)和四个支持核心加强：领导力、标本获取和病理学、临床和生物统计学。这些因素，再加上FH/UW癌症联盟现有的高度互动和跨学科的环境以及对乳腺癌研究的杰出机构支持，确保了乳腺癌翻译孢子计划的成功。

DESCRIPTION (provided by applicant): The Seattle Cancer Consortium (SCC) Breast SPORE application, led by Drs. Peggy Porter and Martin "Mac" Cheever, brings together clinical and laboratory researchers from the Fred Hutchinson Cancer Research Center (FHCRC) and the University of Washington (UW) with a goal to positively impact breast cancer prevention, detection, treatment and care of women who have, or are at risk for, the disease. To achieve that goal, we will carry out strategic research in highly translational projects, develop new research directions as the SPORE progresses, and sponsor new investigators-those starting their careers and those with established careers newly focusing on breast cancer. The investigators in this SPORE view the highly variable response of breast cancers to current therapies as a manifestation of the genotypic and phenotypic heterogeneity of the disease. Therefore, the initial projects on the SPORE will focus on the supposition that targeted treatments need to be focused on the appropriate tumor type. The four major research projects proposed for the Seattle SPORE expand on this theme. Two of the projects are initiated with clinical trials and a focused bed-side-to-bench translational approach. Three of the projects are focused on gaining insight into resistance to therapy and eventually defining what targeted therapies are needed to treat resistant tumors. Project 1 will apply basic discovery of p27kip1 cell cycle regulation in breast cancer to predict mortality and response to therapy. Project 2 will use exquisitely specific and engineered central memory T cells to target abnormally expressed tumor-associated proteins with vaccines and therapy. Project 3 will determine the biological basis for a breast imaging metabolism/perfusion mismatch profile that predicts poor prognosis and poor response to systemic therapy. Project 4 will draw on a well-characterized population-based cohort to identify specific DNA damage pathway biomarkers that could prevent the over, or under, treatment of women with breast cancer. Together, these four projects afford both short- and long-term translational rewards and potential for new discoveries that will impact important aspects of breast cancer care. The SPORE is enhanced by a Developmental Research Program (DRP), a Career Development Program (CDP) and four supporting Cores: Leadership, Specimen Acquisition and Pathology, Clinical, and Biostatistics. These elements, along with the existing highly interactive and interdisciplinary environment and outstanding institutional support for breast cancer research in the FH/UW Cancer Consortium, ensure a successful translational SPORE program in breast cancer.