Seattle Cancer Consortium Breast SPORE

描述（由申请人提供）：西雅图癌症联盟（SCC）乳腺孢子申请，由博士领导。佩吉·波特（Peggy Porter）和马丁·“麦克”·契弗（Martin“Mac”Cheever）将弗雷德·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，目的是积极影响乳腺癌的预防、检测、治疗和护理，帮助患有乳腺癌或有患乳腺癌风险的女性。为了实现这一目标，我们将在具有高度转化性的项目中开展战略研究，随着孢子的进展开发新的研究方向，并资助新的研究人员——那些刚开始从事乳腺癌研究的人员和那些已经建立了职业生涯的人员。本研究的研究人员认为，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，关于SPORE的最初项目将集中于假设靶向治疗需要针对适当的肿瘤类型。为《西雅图孢子》提出的四个主要研究项目都是围绕这个主题展开的。其中两个项目以临床试验和重点从病床边到工作台的转化方法开始。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疗法。项目1将应用p27kip1细胞周期调控在乳腺癌中的基础发现来预测死亡率和对治疗的反应。项目2将使用精确的特异性和工程化的中枢记忆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/灌注错配谱的生物学基础，该谱预测预后不良和对全身治疗的不良反应。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预防乳腺癌妇女的过度或不足治疗。总之，这四个项目提供了短期和长期的转化奖励和潜在的新发现，将影响乳腺癌治疗的重要方面。孢子由一个发展研究计划（DRP），一个职业发展计划（CDP）和四个支持核心：领导力，标本采集和病理学，临床和生物统计学加强。这些因素，加上现有的高度互动和跨学科的环境，以及FH/UW癌症联盟对乳腺癌研究的杰出机构支持，确保了乳腺癌转化孢子项目的成功。

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.