# Project 3: Development of Novel Therapies and Biomarkers for TNBC Patients

> **NIH NIH P50** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $358,272

## Abstract

Project 3: Development of Novel Therapies and Biomarkers for TNBC Patients - Abstract
Triple Negative Breast Cancer (TNBC = Estrogen Receptor-negative, Progesterone Receptor-negative and
HER2-negative) is amongst the most clinically challenging to treat because of its poor prognosis and limited
treatment options. TNBC is a known heterogenous clinical group that shows significant variation based upon
histology, gene expression patterns, response to therapy, and even for patient survival outcomes. Despite this
heterogeneity there are key recurrent biological features of clinical importance including consistently high
proliferation rates, and a likelihood of having immune infiltrates. The typical association with immune cell
features led to the testing, and now approval, of drugs that target the immune system, thus highlighting the
importance of tumor cell to immune cell interactions in TNBC. We will build upon this foundation and our
genomic profiling data coming from human TNBC clinical trials and Genetically Engineered Mouse Models, to
develop and test here new combinatorial therapies for possible use in TNBC, and which will be guided by
biomarker-based patient selection. Specifically, we will evaluate combination regimens with an anti-PD1
backbone containing CD40LG agonist antibody to boost Bcell and/or Dendritic cell function, and combinations
containing drugs that inhibit macrophage function. Lastly, we have identified a unique metabolic vulnerability in
TNBC that is a high dependence upon pyrimidine biosynthesis. Here we will target pyrimidine biosynthesis
alone in mouse models and in human clinical trials, and we will perform combinatorial screens in vitro and in
vivo to identify optimal partner drugs that would synergize with pyrimidine biosynthesis inhibitors. In all cases,
single cell genomics using RNAseq and spatial transcriptomics imaging will be performed in order to inform
about biological responses and to develop and validate biomarkers for future patient selection.

## Key facts

- **NIH application ID:** 10935476
- **Project number:** 2P50CA058223-29A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** CHARLES M PEROU
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $358,272
- **Award type:** 2
- **Project period:** 1997-08-05 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10935476

## Citation

> US National Institutes of Health, RePORTER application 10935476, Project 3: Development of Novel Therapies and Biomarkers for TNBC Patients (2P50CA058223-29A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10935476. Licensed CC0.

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