SPORE: Dana-Farber/Harvard Cancer Center SPORE in Breast Cancer

Dana-Farber/哈佛癌症中心(DF/HCC)乳腺癌孢子中心寻求通过一种综合的、创新的和高度翻译的方法来提高对乳腺癌的理解和治疗。应用程序由四个部分组成 项目和四个核心。项目1汇集了强大的基础科学和人口科学研究人员。它建立在关于雄激素受体(AR)信号的有希望的线索上，并将研究通过AR信号的作用和乳腺癌的发生和进展。研究人员将开发一种新的方法来表征AR信号作为这一努力的一部分。项目2使用最先进的基因工程小鼠模型和尖端临床试验来评估HER2+乳腺癌的耐药机制。它试图通过进一步询问PI3激酶途径来克服这种耐药性，并将评估对PI3激酶抑制剂的敏感性和耐药性。项目3通过开发使精通BRCA的三阴性乳腺癌细胞对PARP抑制敏感的方法来改变目前的范式。该项目建立在坚实的背景之上，包括细胞系、患者衍生的原位异种移植模型和早期临床试验。项目4探索药物开发的“新途径”，评估BET/溴域抑制剂治疗三阴性乳腺癌的作用机制。在强大的临床前阶段之后是一项临床试验，能够了解基因组调节如何影响被诊断为三阴性乳腺癌的患者的预后。每个项目都将对了解乳腺癌的生物学做出重大贡献。这些项目的临床前和临床发现将刺激进一步的研究，并可能产生重大的临床影响。我们的孢子提案使用核心来支持项目，以及DF/HCC社区中的其他研究人员。核心A是科学、财政和行政监督的中心。它将在规划和沟通方面发挥领导作用。它还设有患者倡导委员会，并将监督发展研究计划(DRP)和职业发展计划(CDP)奖项。核心B，生物统计和计算生物学提供了生物统计和基因组数据管理方面的专门知识。核心C，临床试验核心将监督所有与乳房孢子相关的临床试验。它将审查所有方案，协调激活过程，监测临床研究的进行，并与核心D合作促进活检密集型研究。核心D、组织和病理核心将为孢子项目维护组织/血液储存库，在某种程度上，还将为孢子以外的研究人员维护组织/血液储存库。这个核心还将提供病理服务，这些服务对项目中的许多翻译研究目标至关重要。乳腺癌中的DF/HCC孢子由一支由一流的基础、翻译和临床研究人员组成的团队组成，他们由经验丰富和有效的项目主任和高级领导团队领导。DF/HCC孢子准备在未来五年及以后做出重大贡献。

The Dana-Farber/Harvard Cancer Center (DF/HCC) SPORE in Breast Cancer seeks to improve the understanding and treatment of breast cancer with an integrated, innovative, and highly translational approach. The application consists of four Projects and four Cores. Project 1 brings together strong basic- and population-science investigators. It builds upon promising clues about androgen receptor (AR) signaling and will investigate the role of signaling through the AR and the development and progression of breast cancer The investigators will develop a novel approach to characterizing AR signaling as part of this effort. Project 2 uses state-of-the-art genetically engineered mouse models and a cutting edge clinical trial to evaluate resistance mechanisms in HER2+ breast cancer. It seeks to overcome this resistance by further interrogating the PI3 kinase pathway, and will evaluate sensitivity and resistance to PI3 kinase inhibitors. Project 3 shifts current paradigms by the development of approaches that will sensitize BRCA-proficient triple negative breast cancer cells to PARP inhibition. The Project is built upon a solid background including cell lines, patien-derived orthotopic xenograft models, and early phase clinical trials. Project 4 explores a "new avenue" in drug development assessing the mechanisms of action of BET/bromodomain inhibitors for the treatment of triple negative breast cancer. A strong pre-clinical phase is followed by a clinical trial with ability to understand how genomic modulation impacts the outcome of patients diagnosed with triple negative breast cancer. Each Project will contribute substantially to the understanding of the biology of breast cancer. The preclinical and clinical findings from these projects will stimulate further research and could have significant clinical impact. Our SPORE proposal uses Cores to support the Projects, as well as other researchers in the DF/HCC community. Core A is the epicenter of scientific, fiscal and administrative oversight. It will lead efforts in planning and communication. It also houses the Patient Advocacy Committee arid will oversee the Developmental Research Program (DRP) and the Career Development Program (CDP) awards. Core B, Biostatistics and Computational Biology provides specialized expertise in biostatistics and management of genomic data. Core C, Clinical Trials Core will oversee all clinical trials associated with the Breast SPORE. It will review all protocol, coordinate the activation process, monitor the conduct of clinical studies and facilitate biopsy-intensive studies in collaboration with Core D. Core D, Tissue and Pathology Core will maintain tissue/blood repositories for the SPORE Projects and, to some extent, for investigators outside of the SPORE. This Core will also provide pathology services that are critical to many of the translational research aims in Projects. The DF/HCC SPORE in Breast Cancer is comprised of a team of top-notch basic, translational, and clinical investigators who are led by an experienced and effective Program Director and Senior Leadership Team. The DF/HCC SPORE is poised to make substantial contributions over the next five years and beyond.