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Capsaicin and small cell lung cancer therapy

Award Number: R15CA161491
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/09/2012
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Capsaicin and small cell lung cancer therapy - PROJECT SUMMARY Capsaicin is the spicy, pungent ingredient of chili peppers. Conventionally, capsaicin is used as a pain-relieving agent in over-the-counter analgesic creams and lotions. Our research data showed for the first time that capsaicin triggered apoptosis in human small cell lung cancers (SCLCs). However, the development of capsaicin as a feasible anti-cancer drug is limited by its low biological half-life, unpleasant side effects including gut pain, hyperalgesia, stomach cramps and nausea. Biochemical studies have shown that capsaicin analogs containing long chain unsaturated fatty acids in its C-terminal region (called N-AVAMs) were non-pungent and possessed pain-relieving activity. Subsequently, we examined the anti-tumor activity of selected N-AVAM capsaicinoids. We observed that the non-pungent N-AVAM capsaicin analog arvanil displayed greater pro- apoptotic activity relative to capsaicin in human SCLCs. However, arvanil is a viscous liquid with poor solubility properties. Based on the structural motifs of arvanil, the present R15 renewal application proposes structure- activity relationship (SAR) studies to identify capsaicin analogs with improved bioavailability properties and anti- tumor activity and in human SCLCs. Furthermore, arvanil sensitized platinum-resistant human SCLCs to irinotecan-induced apoptosis. The chemosensitization activity of arvanil was greater than capsaicin in human SCLCs. Using these observations as proof-of-concept, the current renewal application will test the chemosensitization ability of a panel of non-pungent N-AVAM capsaicin analogs. The central hypothesis of our renewal application is that the SAR studies will lead to the identification of capsaicinoids which, will display robust anti-tumor activity as single agents and in combination with irinotecan in vivo. In addition, we aim to investigate the bioavailability of these N-AVAM capsaicin compounds in mice models. An innovative feature of our grant application is that we aim to test the anti-tumor activity and chemosensitization activity of these capsaicin analogs in PDX models of human SCLCs. The experimental models outlined in our proposal provide meaningful research experiences for undergraduate and graduate students. The results of our studies will foster the hope of novel therapies in classical and platinum-resistant SCLCs.


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 = $0 )
2026	2021	MARSHALL UNIVERSITY RESEARCH CORPORATION	1 JOHN MARSHALL DR	HUNTINGTON	WV	25755	CABELL	USA	Cancer Cause and Prevention Research	000	3	2/5/2026	COMPETING CONTINUATION	$0
2026	2021	MARSHALL UNIVERSITY RESEARCH CORPORATION	1 JOHN MARSHALL DR	HUNTINGTON	WV	25755	CABELL	USA	Cancer Cause and Prevention Research	001	3	2/5/2026	COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	MARSHALL UNIVERSITY RESEARCH CORPORATION	1 JOHN MARSHALL DR	HUNTINGTON	WV	25755	CABELL	USA	Cancer Cause and Prevention Research	000	3	9/10/2024	COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $427,408 )
2021	2021	MARSHALL UNIVERSITY RESEARCH CORPORATION	ONE JOHN MARSHALL DRIVE	HUNTINGTON	WV	25755	CABELL	USA	Cancer Cause and Prevention Research	001	3	9/14/2021	COMPETING CONTINUATION	$444,000
2021	2016	MARSHALL UNIVERSITY RESEARCH CORPORATION	ONE JOHN MARSHALL DRIVE	HUNTINGTON	WV	25755	CABELL	USA	Cancer Cause and Prevention Research	000	2	8/23/2021	COMPETING CONTINUATION	-$16,592
														Subtotal = $427,408

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2016	MARSHALL UNIVERSITY RESEARCH CORPORATION	ONE JOHN MARSHALL DRIVE	HUNTINGTON	WV	25755	CABELL	USA	Cancer Cause and Prevention Research	000	2	2/12/2020	COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $435,300 )
2016	2016	MARSHALL UNIVERSITY RESEARCH CORPORATION	1050 4TH AVENUE	HUNTINGTON	WV	25701	CABELL	USA	Cancer Cause and Prevention Research	001	2	3/31/2016	COMPETING CONTINUATION	$300,000
2016	2016	MARSHALL UNIVERSITY RESEARCH CORPORATION	1050 4TH AVENUE	HUNTINGTON	WV	25701	CABELL	USA	Cancer Cause and Prevention Research	002	2	4/6/2016	COMPETING CONTINUATION	$135,300
2016	2012	MARSHALL UNIVERSITY RESEARCH CORPORATION	401 11th Street, Suite 1400	HUNTINGTON	WV	25701	CABELL	USA	Cancer Cause and Prevention Research	000	1	3/29/2016	NEW	$0
														Subtotal = $435,300

Issue Date FY: 2012 ( Subtotal = $426,000 )
2012	2012	MARSHALL UNIVERSITY RESEARCH CORPORATION	1050 4TH AVENUE	HUNTINGTON	WV	25701	CABELL	USA	Cancer Cause and Prevention Research	000	1	7/9/2012	NEW	$426,000
														Subtotal = $426,000

Grand Total All Awards = $1,288,708

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Capsaicin and small cell lung cancer therapy

Award Number: R15CA161491

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/09/2012

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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