# Research Project 2 Proteogenomic-guided therapeutic targeting of breast cancer patient-derived xenograft metastases

> **NIH NIH U54** · VIRGINIA COMMONWEALTH UNIVERSITY · 2024 · $254,405

## Abstract

Project Summary/Abstract
Breast cancer is diagnosed in 1-of-8 women and is the most common type of cancer diagnosed at VCU. There
are several genetically distinct subtypes of human breast cancers defined largely based on proliferative status
and expression of targetable receptors such as estrogen receptors and the HER2 oncogene. The majority of
the cell lines and PDX models used for breast cancer research arise from White patients of European
Ancestry, however, all ancestral groups are affected by breast cancers. Over the past twenty years, there has
been a clear disparity identified in the subtype of breast tumors found based on genetic ancestry, with Black
patients being diagnosed more frequently with Basal-like Triple-Negative Breast Cancers, which are highly
metastatic. Therefore, in these studies, we are (1) focused on developing PDX models from breast cancer
patients. With these models we will (2) quantitatively determine their genetic ancestry and then (3) select
models that are genetically Basal-like and obtained from Black patients so that we can (4) use these models to
determine the organs that the colonize, (5) determine the genomic and proteomic profile of the tumors and
metastases, (6) define efficacy of NCI-INDs of interest, with a focus on selinexor based drug combinations on
cells obtained from the PDXs, and (7) identifying new therapeutic drug combinations that are effective in the
metastatic setting. At the conclusion of these studies, we may have identified a new effective two-drug
approach that could be useful for Basal-like patients that have exhausted the current standard-of-care
approaches for treatment of metastatic breast cancer.

## Key facts

- **NIH application ID:** 10890853
- **Project number:** 5U54CA283762-02
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Joshua (Chuck) Harrell
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $254,405
- **Award type:** 5
- **Project period:** 2023-07-19 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890853

## Citation

> US National Institutes of Health, RePORTER application 10890853, Research Project 2 Proteogenomic-guided therapeutic targeting of breast cancer patient-derived xenograft metastases (5U54CA283762-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10890853. Licensed CC0.

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