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

SPORE：丹娜—法伯癌症研究所/哈佛大学癌症中心 SPORE 在乳腺癌中的应用

• 批准号: 8607752
• 负责人: ERIC P WINER
• 金额: $ 215.05万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-17 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8607752
• 关键词: 1-Phosphatidylinositol 3-Kinase; Androgen Receptor; Biology; Biometry; Biopsy; Blood; Breast; Breast Cancer Cell; Breast Cancer Treatment; Bromodomain; Build-it; Cancer Center; Cell Line; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Collaborations; Communication; Communities; Computational Biology; Data; Development; Diagnosis; ERBB2 gene; Genetically Engineered Mouse; Genomics; Goals; Housing; K-Series Research Career Programs; Laboratories; Lead; Leadership; Methods; Monitor; Outcome; PARP inhibition; Pathology; Pathway interactions; Patient advocacy; Patients; Phase; Phosphatidylinositide 3-Kinase Inhibitor; Population Sciences; Process; Protocols documentation; Receptor Signaling; Research; Research Personnel; Resistance; Role; Scientist; Services; Signal Transduction; Solid; Tissues; Translational Research; Xenograft Model; drug development; experience; improved; inhibitor/antagonist; innovation; insight; malignant breast neoplasm; mouse model; next generation; notch protein; novel strategies; pre-clinical; programs; repository; resistance mechanism; translational approach; triple-negative invasive breast carcinoma

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.

Dana-Farber/哈佛癌症中心（DF/HCC）乳腺癌SPORE旨在通过综合，创新和高度转化的方法提高对乳腺癌的理解和治疗。该应用程序包括四个 项目和四个核心。项目1汇集了强有力的基础科学和人口科学调查人员。它建立在关于雄激素受体（AR）信号传导的有希望的线索基础上，并将研究通过AR的信号传导的作用以及乳腺癌的发展和进展。作为这项工作的一部分，研究人员将开发一种新的方法来表征AR信号传导。项目2使用最先进的基因工程小鼠模型和尖端的临床试验来评估HER 2+乳腺癌的耐药机制。它试图通过进一步询问PI 3激酶途径来克服这种耐药性，并将评估对PI 3激酶抑制剂的敏感性和耐药性。项目3通过开发使BRCA-熟练的三阴性乳腺癌细胞对PARP抑制敏感的方法来改变当前的范式。该项目建立在坚实的背景之上，包括细胞系、患者源性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/溴结构域抑制剂治疗三阴性乳腺癌的作用机制。一个强大的临床前阶段之后是一个临床试验，能够了解基因组调控如何影响诊断为三阴性乳腺癌的患者的结果。每个项目都将大大有助于对乳腺癌生物学的理解。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SPORE提案使用Cores来支持项目以及DF/HCC社区的其他研究人员。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主导作用。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，生物统计学和计算生物学提供生物统计学和基因组数据管理的专业知识。核心C，临床试验核心将监督与Breast SPORE相关的所有临床试验。它将审查所有方案，协调启动过程，监测临床研究的开展，并与核心D合作促进活检密集型研究。核心D，组织和病理学核心将为SPORE项目维护组织/血液储存库，并在一定程度上为SPORE以外的研究者维护组织/血液储存库。该核心还将提供病理学服务，这对项目中的许多转化研究目标至关重要。乳腺癌DF/HCC SPORE由一个顶尖的基础，翻译和临床研究人员组成，他们由经验丰富，有效的项目总监和高级领导团队领导。DF/HCC SPORE准备在未来五年及以后做出重大贡献。