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.