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

$68,985U54FY2025CANIH

Hunter College, New York NY

Investigators

Linked publications & trials

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Abstract

Project Summary Partnerships are needed to overcome challenges that have limited systematic biological research on the underpinnings of communities with a higher incidence of aggressive triple negative breast cancer (TNBC). Our U54 partnership augments the ability to study uncommonly studied protein 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 patient breast cancer samples for screening highly probable aggressive breast cancer biomarkers that may facilitate targeted treatments for TNBCs. Moreover, the team will mentor students from HC with cross-organizational exposure to different state-of-the-art scientific platforms to address cancer health balance 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 individuals, to individuals with mtp53/MDM2/MDMX/PARP biomarkers. We will educate individuals experiencing high rates of TNBC 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 European American (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 the community about breast cancer biomarkers. Remove Foundational Limitations to Integration: This study directly addresses persistent issues that have limited biological research on the causes of TNBC. Using biospecimens collected through TUFCCC, the project seeks to identify potential therapeutic targets focused on biomarkers such as mtp53/MDM2/MDMX/PARP. This research experience will help prepare the next generation of scientists through hands-on training and mentorship.

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