# Project 2: Nitric Oxide in the Tumor Micorenviroment of Triple Negative Breast Cancer

> **NIH NIH U54** · UNIVERSITY OF ARIZONA · 2021 · $149,778

## Abstract

PROJECT SUMMARY/ABSTRACT: PROJECT 2
NITRIC OXIDE IN THE TUMOR MICROENVIRONMENT OF TRIPLE NEGATIVE BREAST CANCER
We propose to uncover how tumor produced nitric oxide drives tumor aggressiveness and immune evasion in
triple negative breast cancer (TNBC). We also seek to increase research opportunities in cancer biology for
Native American students. TNBC is an aggressive and metastatic form of breast cancer for which there are no
targeted therapies. TNBC disproportionately affects Native American women and leads to worse outcomes than
for non-Hispanic White women. Overall, Native American women have a 30-70% higher risk of dying from breast
cancer when compared to other ethnicities. Our long-term goals are to develop much-needed new therapies for
TNBC and to increase the pool of Native Americans with a focus on cancer research. Our team brings together
Dr. Narendiran Rajasekaran, an Assistant Professor at Northern Arizona University (NAU) with a strong
background in cancer biology and innate immunity, and Dr. William Montfort, a University of Arizona Cancer
Center Professor with strength in structural biology, therapeutic development and nitric oxide signaling. Our
project meshes with the Partnership for Native American Cancer Prevention (NACP) through our focus on a form
of cancer of high importance to the Native American community, and through our efforts to train emerging Native
American scientists in cancer biology.
Our preliminary data uncover a link between tumor-derived nitric oxide and enhanced hypoxic signaling, which
leads to a gene expression profile favoring tumor promotion, including growth, glycolysis, migration and immune cell
evasion. We have three aims. Aim 1 is to uncover how nitric oxide induces tumor progression, using three breast
cancer cell lines for in vitro work and the 4T1 allograft murine model for in vivo work. Aim 2 is to uncover how
nitric oxide induces tumor evasion of innate immunity through checkpoint blockade involving CD47 and PD-L1,
and cytokine production. Focus is on both macrophages and natural killer cells and will make use of both
xenograft and allograft breast cancer models. Aim 3 is to recruit and train Native American students in cancer
biology and increase the opportunities for cancer research at NAU. Native American students will be recruited
into both laboratories. A particular focus will be on ensuring Prof. Rajasekaran successfully establishes his new
laboratory at NAU with solid student training, funding and publications.

## Key facts

- **NIH application ID:** 10246956
- **Project number:** 5U54CA143924-13
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** WILLIAM R. MONTFORT
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $149,778
- **Award type:** 5
- **Project period:** 2009-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246956

## Citation

> US National Institutes of Health, RePORTER application 10246956, Project 2: Nitric Oxide in the Tumor Micorenviroment of Triple Negative Breast Cancer (5U54CA143924-13). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10246956. Licensed CC0.

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