# Regulation of Tumor Oxygenation by BACH1 in Breast Cancer

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2023 · $398,285

## Abstract

Triple negative breast cancer (TNBC), the most aggressive and metastatic subtype of breast cancer, is one
of the major causes of cancer death in women. TNBC also has lower survival rates for primarily local
cancers. Loss of hormone receptors and the lack of HER2 overexpression in TNBC limit treatments to
cytotoxic therapies such as radiation, a key clinical strategy for 10-15% of breast cancer patients. Hypoxia
is a major cause of resistance to radiotherapy, chemotherapy and even immunotherapy. Thus, identifying
mechanisms to suppress the hypoxia stress response and increase the sensitivity of TNBC tumors to
therapy remains a top clinical priority. Upon hypoxic stress, cancer cells initiate a transcriptional program that
enables them to survive and migrate from an inhospitable microenvironment. While hypoxia-inducible factors
(HIFs) are generally considered the main effectors, growing evidence suggests the hypoxia cellular response is
much more complex and requires coordinated signaling with other stress response factors. One promising
candidate is BACH1, a transcription factor that is induced by hypoxia and represses transcription of genes
involved in heme oxidation and anti-oxidant production. Based on preliminary results, we now hypothesize that
BACH1 is stabilized by hypoxia and functions as a key inducer of the cellular hypoxia response in TNBC
cells leading to abnormal leaky vasculature that contributes to intratumoral hypoxia and radiation
resistance. Specifically, we plan to: 1. Determine whether BACH1 is regulated by oxygen and induces a
transcriptional hypoxic stress response in TNBC cells; 2. Determine whether BACH1 promotes angiogenesis,
leaky vasculature and hypoxia in TNBC tumors; and 3. Determine whether BACH1 depletion sensitizes TNBC
tumors to radiation. We propose that targeting BACH1 represents a unique strategy for increasing tumor
oxygenation to improve the efficacy of cytotoxic, standard-of-care therapies such as radiation. Normalizing
vasculature to suppress leakiness should also facilitate drug delivery to tumors. Since BACH1 can be targeted
by an FDA approved drug either alone or in combination with HIF inhibitors, the proposed work could lead to a
clinical trial in breast cancer and other cancer patients whose treatment involves radiation therapy.

## Key facts

- **NIH application ID:** 10693966
- **Project number:** 5R01CA266643-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** MARSHA R ROSNER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $398,285
- **Award type:** 5
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10693966

## Citation

> US National Institutes of Health, RePORTER application 10693966, Regulation of Tumor Oxygenation by BACH1 in Breast Cancer (5R01CA266643-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10693966. Licensed CC0.

---

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