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

Award Number: K08CA276908
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 06/09/2023
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2027 ( Subtotal = -$52,752 )
2027	2026	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cancer Research Manpower	000	4	10/27/2026	NON-COMPETING CONTINUATION	-$52,752
														Subtotal = -$52,752

Issue Date FY: 2026 ( Subtotal = $251,820 )
2026	2026	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cancer Research Manpower	000	4	5/12/2026	NON-COMPETING CONTINUATION	$251,820
														Subtotal = $251,820

Issue Date FY: 2025 ( Subtotal = $251,820 )
2025	2025	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cancer Research Manpower	000	3	5/19/2025	NON-COMPETING CONTINUATION	$251,820
														Subtotal = $251,820

Issue Date FY: 2024 ( Subtotal = $251,820 )
2024	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cancer Research Manpower	000	2	5/13/2024	NON-COMPETING CONTINUATION	$251,820
														Subtotal = $251,820

Issue Date FY: 2023 ( Subtotal = $253,208 )
2023	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cancer Research Manpower	000	1	6/9/2023	NEW	$253,208
														Subtotal = $253,208

Grand Total All Awards = $955,916

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

Award Number: K08CA276908

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 06/09/2023

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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