# Exploiting Carbon Monoxide Biofoams to Radio-Sensitize Rectal Cancer Cells While Protecting Normal Bowel

> **NIH NIH K08** · UNIVERSITY OF IOWA · 2024 · $251,820

## Abstract

ABSTRACT
An estimated 45,230 individuals were diagnosed with rectal cancer in the United States in 2021. Rectal cancer
is primarily managed using a combination of chemotherapy, radiation, and surgery. Surgical resection of the
rectum is associated with long-term functional deficits and decreased quality-of-life. Therefore, strategies to
improve response to neoadjuvant chemoradiotherapy could increase non-surgical curative rates and enhance
quality-of-life for rectal cancer patients. Carbon monoxide (CO) at low, non-toxic concentrations has been shown
to provide paradoxical anti-tumor effects while inhibiting inflammation and oxidative-stress induced normal tissue
injury that could serve as an adjuvant treatment to enhance chemo-radiotherapy efficacy. CO is a product of
heme catabolism regulated by the Nrf2 transcription factor and the cytoprotective gene Heme Oxygenase-1 (HO-
1). The biochemical mechanisms by which CO simultaneously sensitizes tumor cells to die while preserving
normal cell survival are unknown but likely involve fundamental differences in oxidative metabolism between
cancer and normal cells. Identifying targetable redox sensitive mechanisms underlying the activity of CO in rectal
cancer could rapidly lead to translational therapeutic approaches for improving radiation responses in cancers
while limiting normal tissue injury. We have developed exciting new methods for CO delivery through the
gastrointestinal (GI) tract to overcome the challenges of inhaled CO. Using these GI formulations to deliver CO,
our central hypothesis is that CO, delivered as a safe biofoam, selectively chemo-radio-sensitizes rectal
cancer while reducing normal tissue injury. Further that the mechanism involves differential effects on
Nrf2/HO-1 signaling and modulation of mitochondrial oxidative metabolism. We will evaluate the impact of
cytoprotective CO biofoams on normal rectal tissue responses and oxidative damage after exposure to
chemoradiotherapy and determine the effects of CO as an adjunct to therapy for rectal cancer in mice.

## Key facts

- **NIH application ID:** 10863850
- **Project number:** 5K08CA276908-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** James Donald Byrne
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $251,820
- **Award type:** 5
- **Project period:** 2023-06-09 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10863850

## Citation

> US National Institutes of Health, RePORTER application 10863850, Exploiting Carbon Monoxide Biofoams to Radio-Sensitize Rectal Cancer Cells While Protecting Normal Bowel (5K08CA276908-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10863850. Licensed CC0.

---

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