Breast Cancer Program

乳腺癌筛查（BCP） 项目摘要 乳腺计划（BCP）的主要目标是促进对乳腺癌发展的理解， 乳腺癌的预防和治疗;将实验室发现转化为临床实践; 促进方案内和方案间的互动;并提供丰富的学习 为学生和博士后医学和实验室实习生提供环境。该计划有27 成员（22名研究成员和5名临床成员），并与细胞信号传导和 代谢计划和一名成员与癌症细胞和基因治疗计划。杰弗里罗森博士是 BCP领导人和共同领导人Mothaffar Rimawi，MD。BCP包括一个强大的基础科学小组， 一个临床乳房中心，拥有一个大型和积极的临床和翻译计划。截至2019年7月，该计划 直接供资总额为1 740万美元，其中1 420万美元经过同行审查，包括来自 NCI在过去的5年里，该计划的成员发表了301篇与癌症有关的论文， 其中36%的期刊为计划内期刊，21%为计划间期刊，65%为机构间期刊 合作。BCP围绕4个研究主题组织：（1）干细胞，（2）治疗抗性， (3)串扰和信号传导，和（4）转移和肿瘤微环境。翻译到诊所， 所有这些主题的一个组成部分。我们的临床试验组合是强大的和高度转化的。我们 研究人员设计并领导了国家和国际试验，这些试验有可能改变我们 了解和治疗乳腺癌。BCP研究人员将几项实验室发现转化为 国家和国际临床试验，包括2项合作组水平的试验，2项TBCRC试验， 一个全球性的试验。这些试验的影响可能会改变我们治疗乳腺癌的方式。主要 BCP的成就是：（1）蛋白质基因组学作为发现和诊断的发展 一种可以识别耐药晚期乳腺癌新治疗靶点和假设的工具，（2） 靶向未折叠蛋白应答的新型小分子治疗剂的开发 与乳腺癌化疗，（3）新的见解的作用，RNA剪接在乳腺癌 进展其他成就包括：研究确认对内分泌和HER 2的耐药性机制 靶向治疗，构建一个独特的多参数分子分类器，以确定患者， 肿瘤可以安全地单独用靶向治疗，识别新的靶向弱点， 三阴性乳腺癌（TNBC），阐明了参与骨微转移的信号级联， 以及有助于对免疫检查点的治疗应答的2种“骨髓亚型”的定义 在TNBC的封锁。其中的一些意见已经形成了更新专业计划的基础 卓越研究（SPORE）申请已经连续资助了27年。

BREAST CANCER PROGRAM (BCP) PROJECT SUMMARY The main goals of the Breast Program (BCP) are to advance the understanding of breast cancer development, and the prevention and treatment of breast cancer; to translate laboratory discoveries to clinical practice; to facilitate intra-programmatic and inter-programmatic interactions; and to provide an enriched learning environment for students and postdoctoral medical and laboratory-based trainees. The Program has 27 members (22 Research members and 5 Clinical members) and shares 2 members with the Cell Signaling and Metabolism Program and one member with Cancer Cell and Gene Therapy Program. Jeffrey Rosen, PhD is the Leader of BCP, and Mothaffar Rimawi, MD, the Co-Leader. BCP includes both a strong basic science group and a clinical breast center that has a large and active clinical and translational program. As of July 2019, the Program has total direct funding of $17.4 million, of which $14.2 million is peer reviewed including $6.3 million from the NCI. In the last 5 years, members of the Program published 301 cancer-related manuscripts in peer-reviewed journals of which 36% represented intra-programmatic, 21% inter-programmatic, and 65% inter-institutional collaborations. The BCP is organized around 4 Research Themes: (1) Stem Cells, (2) Treatment Resistance, (3) Cross Talk and Signaling, and (4) Metastasis and the Tumor Microenvironment. Translation to the clinic is an integral component of all of these Themes. Our clinical trial portfolio is robust and highly translational. Our investigators designed and led national and international trials that have the potential to alter the way we understand and treat breast cancer. BCP investigators translated and led several laboratory discoveries into national and international clinical trials including 2 trials at the cooperative group level, 2 trials with the TBCRC, and one global trial. The impact of those trials is likely to alter the way we treat breast cancer. Major accomplishments of the BCP are: (1) The development of proteogenomics as both a discovery and diagnostic tool that may identify new therapeutic targets and hypotheses in treatment-resistant advanced breast cancer, (2) The development of novel small molecule therapeutics to target the unfolded protein response in combination with chemotherapy in breast cancer, and (3) New insights into the role of RNA splicing in breast cancer progression. Other achievements include: studies to confirm mechanisms of resistance to endocrine and HER2 targeted therapies, the construction of a unique multiparameter molecular classifier to identify patients whose tumors can be safely treated with target therapy alone, the identification of novel targetable vulnerabilities in triple-negative breast cancer (TNBC), the elucidation of signaling cascades involved in bone micrometastasis, and the definition of 2 “myeloid subtypes” that contribute to the therapeutic response to immune checkpoint blockade in TNBC. Several of these observations have formed the basis for the renewal of a Specialized Program of Research Excellence (SPORE) application that has been continuously funded for 27 years.