SPORE in Breast Cancer

项目总结/摘要：总体 这是Vanderbilt-Ingram癌症中心（VICC）的第三个竞争性更新申请。 癌使用非常活跃和强大的多学科VICC乳腺癌的完善框架 该计划得到了SPORE机制的大力支持，我们在目前的工作中取得了重大进展。 项目期间。我们非常成功的发展研究项目（DRP）和职业提升 项目（CEP）继续催化转化乳腺癌研究中的新想法和新研究者， 包括两个项目在这一持续更新。我们有能力完成拟议的工作， 在未来的几年里，由于一个特殊的多学科计划， 与其他乳腺癌项目和SPORE以及国家和 国际合作。我们的总体目标仍然是一样的：开展合作，多学科和 以机制为基础的转化研究，将对患有或 有患乳腺癌的风险经过重要的规划和内部和外部咨询委员会的评估，我们 提出四个双向翻译项目，解决基础，翻译和临床研究问题 项目1和2是继续项目，项目3和4是新项目 在本供资周期内，从两个CEP奖演变而来的项目： ER+乳腺癌对内分泌治疗的耐药性;项目2 -改善TNBC结局的策略 整合亚型特异性基因组和基于免疫的发现的患者;项目3 -靶向DNA 乳腺癌的损伤反应;项目4 -靶向抗原呈递以改善免疫治疗 乳腺癌的治疗该应用程序还包括DRP和CEP，以及四个高度集成的共享 核心资源：管理和参与，生物统计学和生物信息学，病理学和组织 信息学和免疫表型。核心带来创新的技术和资源，包括额外的 具有项目特定专业知识的人员，整个VICC乳腺孢子计划，不要重复预 VICC或范德比尔特大学医学中心（VUMC）的现有共享资源。重点是 人类终点，六项介入治疗临床试验与高度转化的项目相关 在该提案中，所有这些都基于世界一流的基础和临床研究人员之间的广泛合作。我们 已经牢固地建立了一个真正的多学科团队，成功地实施了创新的临床试验， 从体外和患者研究中得出的假设，将继续产生富有成效的翻译， 与其他乳腺癌计划和SPORE以及国家和国际团体合作。

PROJECT SUMMARY/ABSTRACT: OVERALL This is the third competing renewal application of the Vanderbilt-Ingram Cancer Center (VICC) SPORE in Breast Cancer. Using the well-established framework of a very active and strong multidisciplinary VICC Breast Cancer Program that is robustly supported by the SPORE mechanism, we have made significant progress in our current project period. Our highly successful Developmental Research Projects (DRP) and Career Enhancement Programs (CEP) continue to catalyze new ideas and new investigators in translational breast cancer research, including two projects in this continuing renewal. We are uniquely poised to complete the proposed work and to be even more productive in the years to come, thanks to an exceptional multidisciplinary program and established productive collaborations with other Breast Cancer Programs and SPOREs, as well as national and international collaborations. Our overall goal remains the same: To conduct collaborative, multidisciplinary and mechanism-based translational research that will have the highest possible impact for women and men with or at risk for breast cancer. After significant planning and internal and external advisory board evaluation, we propose four bi-directional translational projects addressing basic, translational and clinical research questions of importance in human breast cancer; Projects 1 and 2 are continuation projects, Projects 3 and 4 are new projects that have evolved from two CEP awards in the current funding cycle: Project 1 - Mechanisms of Resistance to Endocrine Therapy in ER+ Breast Cancer; Project 2 - Strategies to Improve Outcomes for TNBC Patients Integrating Subtype-specific Genomic and Immune-based Discoveries; Project 3 - Targeting the DNA Damage Response in Breast Cancer; Project 4 - Targeting Antigen Presentation to Improve Immunotherapy Responses in Breast Cancer. The application also includes DRP and CEP, and four highly integrated shared core resources: Administration and Engagement, Biostatistics and Bioinformatics, Pathology and Tissue Informatics, and Immunophenotyping. The cores bring innovative technology and resources, including additional personnel with project-specific expertise, to the overall VICC Breast SPORE Program and do not duplicate pre- existing shared resources available at VICC or Vanderbilt University Medical Center (VUMC). With a focus on human endpoints, six interventional therapeutic clinical trials are associated with the highly translational projects in this proposal, all based on extensive collaboration between world-class basic and clinical investigators. We have firmly established a true multidisciplinary team that successfully implements innovative clinical trials to test hypotheses that result from in vitro and patient studies, and that will continue to have productive translational collaborations with other Breast Cancer Programs and SPOREs as well as national and international groups.