Breast Cancer Program

乳腺癌计划

• 批准号: 10439824
• 负责人: Jeffrey Mark Rosen
• 金额: $ 3.26万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10439824
• 关键词: Achievement; Animal Model; Basic Science; Breast; Breast Cancer Treatment; Cancer Center; Cancer Center Support Grant; Cell Line; Cell Therapy; Cellular Metabolic Process; Clinic; Clinical; Clinical Trials; Collaborations; Development; Doctor of Philosophy; ERBB2 gene; Endocrine; Faculty; Funding; Genetically Engineered Mouse; Goals; Human; Immune system; Immunocompetent; Immunotherapy; International; Journals; Laboratories; Malignant Neoplasms; Manuscripts; Medical; Medicine; Micrometastasis; Modeling; Molecular; Myelogenous; Neoplasm Metastasis; Pathway interactions; Patients; Peer Review; Postdoctoral Fellow; Prevention; Proteins; Publishing; RNA Splicing; Recurrence; Regimen; Research; Research Personnel; Resistance; Role; Signal Pathway; Signal Transduction; Specialized Program of Research Excellence; Students; Testing; Translating; Translations; advanced breast cancer; base; bone; breast cancer progression; cancer cell; career development; chemotherapy; clinical practice; college; design; diagnostic tool; educational atmosphere; gene therapy; immune checkpoint blockade; insight; inter-institutional; malignant breast neoplasm; mammary gland development; member; new therapeutic target; novel; novel therapeutics; patient derived xenograft model; pre-clinical; programs; proteogenomics; recruit; resistance mechanism; response; small molecule therapeutics; standard of care; stem cells; targeted treatment; therapy resistant; treatment response; triple-negative invasive breast carcinoma; tumor; tumor microenvironment; tumor progression

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.

乳腺癌计划（BCP） 项目摘要 乳房计划（BCP）的主要目标是提高对乳腺癌发展的理解， 以及乳腺癌的预防和治疗；将实验室发现转化为临床实践； 促进策略内和编程间相互作用；并提供丰富的学习 学生和博士后医学和实验室的学员的环境。该程序有27 成员（22名研究成员和5名临床成员），并与3个成员分享了细胞信号和 代谢计划和一名癌细胞和基因治疗计划的成员。杰弗里·罗森（Jeffrey Rosen），博士是 BCP的负责人和马里兰州Mothafar Rimawi，共同领导者。 BCP既包括一个强大的基础科学小组，又包括 一个临床乳房中心，具有大型且活跃的临床和翻译程序。截至2019年7月，该计划 总直接资金为1,740万美元，其中1,420万美元的同行审查，其中包括630万美元 NCI。在过去的五年中，该计划的成员在同行评审中发布了301项与癌症有关的手稿 其中36％的期刊代表了前编程，21％的程序间和65％的机构间 协作。 BCP围绕4个研究主题组织：（1）干细胞，（2）治疗性， （3）串扰和信号传导，以及（4）转移和肿瘤微环境。翻译到诊所的是 所有这些主题的组成部分。我们的临床试验组合很健壮且翻译高度。我们的 调查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的方式 了解和治疗乳腺癌。 BCP调查人员翻译并带领一些实验室发现 国家和国际临床试验，包括合作小组级别的2个试验，与TBCRC进行了2次试验， 和一项全球审判。这些试验的影响可能会改变我们治疗乳腺癌的方式。主要的 BCP的成就是：（1）蛋白质组学作为发现和诊断的发展 可以识别耐药晚期乳腺癌中新的治疗靶标和假设的工具，（2） 新型小分子疗法的发展以靶向结合的展开蛋白质反应 通过化学疗法在乳腺癌中，以及（3）对RNA剪接在乳腺癌中作用的新见解 进展。其他成就包括：确认对内分泌和HER2抗性机制的研究 有针对性的疗法，建造独特的多参数分子分类器，以鉴定患者 肿瘤可以单独使用靶疗法安全治疗 三阴性乳腺癌（TNBC），阐明涉及骨微量含量的信号传导级联反应， 以及2个有助于免疫检查点的治疗反应的“髓样亚型”的定义 TNBC中的桶。这些观察中的几个构成了续签专业计划的基础 卓越的研究（孢子）应用程序已连续资助了27年。