# Intratumoral Heterogeneity and Plasticity in Basal-Like Breast Cancers

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $40,410

## Abstract

Project Summary
Triple Negative Breast Cancer (TNBC) is an aggressive malignancy with a poor prognosis that accounts for 10-
20% of breast cancer cases worldwide. Tumor resistance to chemotherapy is a major obstacle facing patients
with TNBCs, as TNBCs lack conventional druggable targets and patients rely on chemotherapy as the main
treatment option. Intra-tumoral heterogeneity and tumor cell plasticity are thought to contribute to resistance to
chemotherapy. Basal-like breast cancer (BLBC) is a molecular subtype that makes up ~70% of TNBCs, and is
characterized by high heterogeneity and genetically diverse tumor cells. The mechanism by which BLBC tumor
cells develop resistance to chemotherapy is poorly understood. I hypothesize that plasticity between tumor cell
phenotypic states, specifically basal-like and mesenchymal states, leads to changes in tumor sensitivity to
chemotherapy.
This work aims to identify the genetic regulators of plasticity between subpopulations of BLBCs and to test
whether targeted agents blocking or initiating this plasticity can lead to changes in tumor chemo-sensitivity. To
do this, my first aim is to identify the functional and genomic characteristics of distinct cellular subpopulations in
BLBCs by flow cytometry and single cell RNA-sequencing (scRNA-seq), using murine and human TNBC models
in vivo. I will use gene expression and network analyses to identify possible genetic regulators of each
subpopulation, and test these empirically using CRISPR knockouts. In the second aim, I plan to test whether
chromatin remodeling inhibitors are able to block EMT in BLBC tumors and thereby increase tumor sensitivity to
chemotherapy. This work is expected to identify potential inherent and therapy-induced regulators of tumor
plasticity, which could have therapeutic implications in developing improved treatment regimens for patients with
chemo-resistant TNBCs.

## Key facts

- **NIH application ID:** 10348711
- **Project number:** 5F31CA257166-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Cherise Ryan Glodowski
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $40,410
- **Award type:** 5
- **Project period:** 2021-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10348711

## Citation

> US National Institutes of Health, RePORTER application 10348711, Intratumoral Heterogeneity and Plasticity in Basal-Like Breast Cancers (5F31CA257166-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10348711. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*