Seattle Cancer Consortium Breast SPORE

描述（申请人提供）：由Peggy Porter和Martin“Mac”Cheever博士领导的西雅图癌症联盟（SCC）Breast SPORE应用程序汇集了来自Fred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，目标是积极影响乳腺癌预防，检测，治疗和护理患有或有风险的女性，这种疾病为了实现这一目标，我们将在高度转化的项目中进行战略研究，随着SPORE的进展开发新的研究方向，并赞助新的研究者-那些开始他们的职业生涯和那些新近专注于乳腺癌的职业生涯。本SPORE的研究人员认为，乳腺癌对当前治疗的高度可变反应是该疾病基因型和表型异质性的表现。因此，SPORE的初始项目将集中在靶向治疗需要集中在适当的肿瘤类型的假设上。为西雅图孢子提出的四个主要研究项目扩展了这一主题。其中两个项目是通过临床试验和集中的床旁到工作台转化方法启动的。其中三个项目的重点是深入了解对治疗的耐药性，并最终确定治疗耐药肿瘤所需的靶向治疗。项目1将应用乳腺癌p27 kip 1细胞周期调控的基本发现来预测死亡率和对治疗的反应。项目2将使用精细特异性和工程化的中央记忆T细胞，通过疫苗和治疗靶向异常表达的肿瘤相关蛋白。项目3将确定乳腺成像代谢/灌注不匹配特征的生物学基础，该特征可预测不良预后和对全身治疗的不良反应。项目4将利用一个充分表征的基于人群的队列来确定特定的DNA损伤途径生物标志物，这些生物标志物可以防止乳腺癌女性的过度或不足治疗。总之，这四个项目提供了短期和长期的转化回报和新发现的潜力，这将影响乳腺癌护理的重要方面。SPORE由发展研究计划（DRP），职业发展计划（CDP）和四个支持核心增强：领导力，标本采集和病理学，临床和生物统计学。这些因素，沿着现有的高度互动和跨学科的环境和杰出的机构支持乳腺癌研究在FH/UW癌症联盟，确保成功的翻译孢子计划在乳腺癌。

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.