Pilot Research Project: Evaluating Black and African American Breast Cancer Populations for Therapeutic Targeting of Aberrant p53, MDM2, MDMX, and PARP signaling

项目摘要 评估黑人和非裔美国人乳腺癌患者的治疗效果 靶向异常的p53、MDM2、MDMX和PARP信号转导 合著者：吉尔·巴戈内蒂博士(联席领导) TUfccc：Denise Connolly博士(联席领导) 需要伙伴关系来打破限制了系统性和道德性的系统性障碍。 侵袭性三阴性乳腺癌(TNBC)的生物学基础研究 非洲裔美国黑人(AA)。我们的U54伙伴关系提高了学习的能力 生物标志物研究不足，以改进筛查和治疗选择。这架U54飞行员 该项目汇集了亨特学院(HC)和坦普尔的知名科学家团队 大学福克斯大通癌症中心(TUfcc)分析已有的AA患者乳房 用于筛选高度可能的侵袭性乳腺癌生物标记物的癌症样本 促进针对再障TNBCs的靶向治疗。此外，团队将指导代表人数不足的人 来自HC的学生跨机构接触到不同最先进的科学平台 在培训和研究目标中解决癌症健康公平问题。的主要目标是 这个项目是为了确定PARP抑制剂(PARPI)疗法是否可以扩大， 超越突变的BRCA1队列，到带有mtp53/MDM2/MDMX/PARP的Black/AA队列 生物标志物。我们将教育黑人/AA社区有关乳腺癌生物标记物的知识，并将 使他们能够在诊断和治疗期间提出基于生物标记物的问题。我们的目标是 以下是。1)比较MDM2、MDMX、mtP53和PARP在乳腺癌中的表达 (BC)来自AA和EA患者的肿瘤。我们将构建(BC)组织微阵列(TMA) 回顾性收集125例AA和125例EA患者的肿瘤资料。TMA将被染成 MDM2、MDMX、P53和PARP。2)我们将测试MDM2/MDMX-mtp53-PARP的驱动因素 用于在细胞培养和异种小鼠模型中以PARPI疗法靶向BCS。我们会工作的 与社区外展核心一起教育社区有关乳腺癌生物标记物的知识 打破纳入的系统性障碍：这项研究直接针对再生障碍性疾病的系统性障碍 女性作为TNBC生物学决定因素的未被研究的队列。我们正在整理TUfccc BC AA样本，目的是确定潜在的靶向治疗方案以减少乳房 癌症差异。这项工作的完成将为重症乳腺癌的研究提供深入的见解 生物标记物mtp53/MDM2/MDMX/PARP在Black/AAs中的应用，并将教育下一代 未被充分代表的科学家。

Project Summary Evaluating Black and African American Breast Cancer Populations for Therapeutic Targeting of Aberrant p53, MDM2, MDMX, and PARP signaling HC: Jill Bargonetti, PhD (Co-Leader) TUFCCC: Denise Connolly, PhD (Co-Leader) Partnerships are needed to break the systemic barriers that have limited systematic and ethical biological research on the underpinnings of aggressive triple negative breast cancer (TNBC) in Black Americans of African Ancestry (AA). Our U54 partnership increases the ability to study understudied biomarkers in order to improve screening and treatment options. This U54 pilot project brings together teams of established scientists at Hunter College (HC) and Temple University Fox Chase Cancer Center (TUFCCC) to analyze already available AA patient breast cancer samples for screening highly probable aggressive breast cancer biomarkers that may facilitate targeted treatments for AA TNBCs. Moreover, the team will mentor underrepresented students from HC with cross-institutional exposure to different state of the art scientific platform to Address Cancer Health Equity in training as well as research objectives. The primary goal of this project is to determine if PARP inhibitor (PARPi) therapeutics can be expanded, beyond the mutant BRCA1 cohorts, to Black/AA cohorts with mtp53/MDM2/MDMX/PARP biomarkers. We will educate the Black/AA community about breast cancer biomarkers and will empower them to ask biomarker-based questions during diagnosis and treatment. The aims are the following. 1) To compare the expression of MDM2, MDMX, mtp53 and PARP in breast cancer (BC) tumors from AA and EA patients. We will construct (BC) tissue microarrays (TMAs) from retrospectively collected tumors from 125 AA and 125 EA patients. TMAs will be stained for MDM2, MDMX, p53 and PARP. 2) We will test the driver roles of the MDM2/MDMX-mtp53-PARP for targeting BCs with PARPi therapies in cell culture and xenograft mouse models. We will work with the Community Outreach Core to educate community about breast cancer biomarkers Break Systemic Barriers to Inclusion: This study directly addresses systemic barriers of AA women as an understudied cohort for biological determinants of TNBC. We are collating TUFCCC BC AA samples, with the goal of identifying potential targeted therapeutic options to reduce breast cancer disparities. Completion of this work will provide insights on critical breast cancer biomarkers mtp53/MDM2/MDMX/PARP in Black/AAs and will educate the next generation of under-represented scientists.