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Chemoprevention of head and neck cancer using combination of natural compounds

Award Number: R03DE036365
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2028

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Chemoprevention of head and neck cancer using combination of natural compounds - PROJECT SUMMARY Head and neck squamous cell carcinoma (HNSCC) is a devastating disease with significant morbidity and mortality; 72,680 projected new cases and 16,680 deaths in the US in 2025. Delaying and preventing the progression of premalignant lesions to invasive cancer by chemoprevention can save thousands of lives; currently no such treatment regimen is available. An effective chemoprevention method implemented before invasive cancer develops is warranted to reduce the incidence of HNSCC. This research will investigate the use of diet-derived natural compounds EGCG and resveratrol as a novel combination for chemoprevention of this deadly cancer. Carcinogenesis initiates with an irreversible genetic mutation caused by endogenously-derived or carcinogen-induced oxidative stress when physiological repair mechanisms fail. The transcription factor NRF- 2 is activated in response to oxidative stress and essential for detoxifying carcinogens and carcinogen-induced oxidative stress, thus compounds capable of activating this pathway are suitable for chemoprevention. The combination of EGCG and resveratrol demonstrates activation of genes associated with xenobiotic metabolism and antioxidant defense against oxidative stress. In this proposal, we will develop the combination of resveratrol and EGCG as a regimen for the chemoprevention of HNSCC. Our previously published data demonstrates that the combination of EGCG and resveratrol induces synergistic apoptosis and more effectively inhibits HNSCC xenografts in nude mice that any single agent by inhibiting the AKT-mTOR pathway. More importantly, the combination also significantly inhibits 4NQO-induced oral carcinogenesis in mice. This proposal will test the ability of the combination of EGCG and resveratrol to prevent or delay the development and progression of oral lesions in carcinogen-induced oral cancer models in a GDF15-dependent manner and uncover the cell signaling mechanism(s) of action for this agent. We hypothesize that the combination of EGCG and resveratrol induces chemopreventive effect by activating the antioxidant and the xenobiotic metabolism pathways and by upregulating the expression of GDF15. Two specific aims are proposed. Aim 1: Demonstrate the molecular pathway for chemoprevention of HNSCC by EGCG and resveratrol. We will study the role of the NRF2- mediated oxidative stress pathway that ameliorates carcinogen-induced oxidative stress and mutagenicity. Aim 2: Explore the role of GDF15 in 4-NQO-induced oral carcinogenesis and chemoprevention by the combination of resveratrol and EGCG. 4-NQO-induced oral cancer in mice will evaluate the role of GDF15 in oral carcinogenesis and the prevention or delay in oral carcinogenesis with the administration of EGCG and resveratrol. The outcome of the in vivo studies will confirm the chemoprevention effects of the combination of EGCG and resveratrol in HNSCC and will pave the way for further clinical development of this novel combination.


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: 2026 ( Subtotal = $295,000 )
2026	2026	MARSHALL UNIVERSITY RESEARCH CORPORATION	1 JOHN MARSHALL DR	HUNTINGTON	WV	25755	CABELL	USA	Oral Diseases and Disorders Research	000	1	7/23/2026	NEW	$295,000
														Subtotal = $295,000

Grand Total All Awards = $295,000

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Chemoprevention of head and neck cancer using combination of natural compounds

Award Number: R03DE036365

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/01/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2028

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