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Developing new therapeutic strategies against head and neck cancer

Award Number: R01DE025141
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: 02/15/2015
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Developing new therapeutic strategies against head and neck cancer - Abstract Head and neck cancer (HNC) is the sixth most prevalent cancer in the world, and oral cancer is the most common subtype. The World Health Organization estimates ~330,000 deaths per year globally. The overall survival rate (50-60%) has not improved over the past couple of decades, despite significant improvements in surgical procedure, radiotherapy, and chemotherapy. The risk factors associated with oral cancer includes tobacco use, excessive alcohol consumption, betel quid chewing, and human papillomavirus (HPV) infection. HPV infection is likely to be reduced in the future due to successful vaccination and better prognosis. There is a critical need to define the HNC disease processes, and to identify better therapeutic strategies for successful HNC patient management. Further, non-traditional therapies must be investigated as adjuncts to reduce the risk of recurrence and improve survival. In our current funding period, we made several important novel observations. We showed that bitter melon extract feeding alters c-Met signaling and prevents HNC growth in preclinical models. We subsequently showed an immunomodulatory role of bitter melon extract, although the precise mechanism is yet to be determined. Further, we found several long non-coding RNAs are altered in feeding of bitter melon extract in a carcinogen-induced model. Very recently, we identified momordicine-I, one of the active metabolites of bitter melon, which shows therapeutic anti-tumor activity in an oral cancer preclinical model. Although we gained much evidence for bitter melon in prevention of HNC from our and other studies, considerable knowledge gaps remain in understanding the mechanism of momordicine-I on tumor metabolism and immune regulation, and its therapeutic use. Based on our and others results, we hypothesize that combining momordicine-I with other current therapeutics will improve efficacy in tumor regression. We will also examine the changes in glucose and lipid metabolism and the tumor microenvironment after treatment with momordicine-I using a mouse model. Results from this study will have important translational implications and significant benefits along with current therapy. Innovation: Our study will examine for the first time the therapeutic and mechanistic effects of momordicine-I in HNC animal models for major translational impact.


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: 2025 ( Subtotal = $480,690 )
2025	2025	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Oral Diseases and Disorders Research	000	9	3/28/2025	NON-COMPETING CONTINUATION	$432,620
2025	2025	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Oral Diseases and Disorders Research	001	9	5/8/2025	NON-COMPETING CONTINUATION	$48,070
														Subtotal = $480,690

Issue Date FY: 2024 ( Subtotal = $471,077 )
2024	2024	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Oral Diseases and Disorders Research	000	8	3/12/2024	NON-COMPETING CONTINUATION	$432,620
2024	2024	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Oral Diseases and Disorders Research	001	8	6/6/2024	NON-COMPETING CONTINUATION	$38,457
														Subtotal = $471,077

Issue Date FY: 2023 ( Subtotal = $483,667 )
2023	2023	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Oral Diseases and Disorders Research	002	7	2/28/2023	NON-COMPETING CONTINUATION	$483,667
2023	2022	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Oral Diseases and Disorders Research	001	6	11/9/2022	COMPETING CONTINUATION	$26,415
2023	2019	SAINT LOUIS UNIVERSITY	221 N GRAND BLVD	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Oral Diseases and Disorders Research	000	5	11/9/2022	NON-COMPETING CONTINUATION	-$26,415
														Subtotal = $483,667

Issue Date FY: 2022 ( Subtotal = $436,022 )
2022	2022	SAINT LOUIS UNIVERSITY	ONE NORTH GRAND	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Oral Diseases and Disorders Research	002	6	2/14/2022	COMPETING CONTINUATION	$434,870
2022	2022	SAINT LOUIS UNIVERSITY	ONE NORTH GRAND	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Oral Diseases and Disorders Research	003	6	3/23/2022	COMPETING CONTINUATION	$1,152
2022	2019	SAINT LOUIS UNIVERSITY	ONE NORTH GRAND	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Oral Diseases and Disorders Research	001	5	2/8/2022	NON-COMPETING CONTINUATION	$0
2022	2019	SAINT LOUIS UNIVERSITY	ONE NORTH GRAND	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Oral Diseases and Disorders Research	000	5	11/9/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $436,022

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	SAINT LOUIS UNIVERSITY	ONE NORTH GRAND	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Oral Diseases and Disorders Research	000	5	1/8/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $378,750 )
2019	2019	SAINT LOUIS UNIVERSITY	ONE NORTH GRAND	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Oral Diseases and Disorders Research	000	5	1/17/2019	NON-COMPETING CONTINUATION	$378,750
														Subtotal = $378,750

Issue Date FY: 2018 ( Subtotal = $378,750 )
2018	2018	SAINT LOUIS UNIVERSITY	ONE NORTH GRAND	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Oral Diseases and Disorders Research	000	4	1/9/2018	NON-COMPETING CONTINUATION	$340,875
2018	2018	SAINT LOUIS UNIVERSITY	ONE NORTH GRAND	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Oral Diseases and Disorders Research	001	4	4/20/2018	NON-COMPETING CONTINUATION	$37,875
														Subtotal = $378,750

Issue Date FY: 2017 ( Subtotal = $378,750 )
2017	2017	SAINT LOUIS UNIVERSITY	ONE NORTH GRAND	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Oral Diseases and Disorders Research	001	3	5/26/2017	NON-COMPETING CONTINUATION	$37,875
2017	2017	SAINT LOUIS UNIVERSITY	ONE NORTH GRAND	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Oral Diseases and Disorders Research	000	3	1/18/2017	NON-COMPETING CONTINUATION	$340,875
														Subtotal = $378,750

Issue Date FY: 2016 ( Subtotal = $378,750 )
2016	2016	SAINT LOUIS UNIVERSITY	3500 LINDELL BLVD/FITZG'D HALL	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Oral Diseases and Disorders Research	000	2	2/2/2016	NON-COMPETING CONTINUATION	$378,750
														Subtotal = $378,750

Issue Date FY: 2015 ( Subtotal = $378,750 )
2015	2015	SAINT LOUIS UNIVERSITY	3500 LINDELL BLVD/FITZG'D HALL	SAINT LOUIS	MO	63103	SAINT LOUIS CITY	USA	Oral Diseases and Disorders Research	000	1	2/13/2015	NEW	$378,750
														Subtotal = $378,750

Grand Total All Awards = $3,765,206

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Developing new therapeutic strategies against head and neck cancer

Award Number: R01DE025141

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: 02/15/2015

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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