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Artemin overexpression in oral cancer pain and carcinogenesis

Award Number: R01CA228525
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2019
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Artemin overexpression in oral cancer pain and carcinogenesis - Oral cancer patients suffer severe chronic and mechanically-induced pain. Opioids are initially effective, but dose escalation is required and side effects reduce quality of life. The long-term goal is to improve management of oral cancer and oral cancer pain. Oral cancer pain is initiated and maintained in the cancer microenvironment. Some overexpressed cancer genes, oncogenes, can function in an autocrine manner to promote cancer and in a paracrine manner as cancer pain mediators. The ensemble of altered genes/pathways in a cancer dictates response to treatment, which motivates the use of combinatorial therapies tailored to the individual (precision medicine) to both treat the cancer and pain. The overall objectives of this application are to determine (a) whether artemin (ARTN), a gene overexpressed in oral cancer is an oral cancer oncogene, (b) whether ARTN is an oral cancer pain mediator and (c) whether antagonizing ARTN stops oral cancer and alleviates oral cancer pain. The central hypothesis is that there are oral cancer oncogenes that promote cancer and induce oral cancer pain. The rationale for this project is that proalgesic oncogenes could be targeted to treat cancer and pain. The central hypothesis will be tested by pursuing three specific aims: (1) Determine if ARTN is a proalgesic oncogene in human cancer; (2) Determine whether ARTN is an oncogene and a nociceptive mediator; and (3) Determine the potential to stop oral cancer and alleviate oral cancer pain by antagonizing proalgesic oncogenes. In the first aim, expression of ARTN will be assessed by immunohistochemistry in archival specimens from patients who completed the UCSF Oral Cancer Pain Questionnaire (UCSFOCPQ) to determine if expression is correlated with pain. The second aim will evaluate the function of ARTN as an oncogene by manipulating expression in cultured cells in vitro and in human xenograft mouse models. Whether ARTN is a pain mediator will be assessed by measuring nociception induced by manipulating expression of ARTN in animal models in the absence of cancer growth. For the third aim, the potential of antagonizing ARTN to stop cancer and cancer pain will be evaluated by anti-ARTN treatment of mouse xenograft and carcinogenesis models. The proposed research is innovative in the applicants' opinion, because it uses information gained from genomic analysis of oral cancers to identify putative oral cancer proalgesic oncogenes. The research is significant because it is expected to lay the foundation for future clinical trials assessing the utility of targeting ARTN for cancer treatment and attenuation of cancer pain. The work will motivate identification of additional proalgesic oncogenes to improve precision cancer pain management.


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	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S FL 11	NEW YORK	NY	10012	NEW YORK	USA	Cancer Treatment Research	000	6	1/5/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $306,247 )
2024	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Cancer Treatment Research	000	6	7/16/2024	NON-COMPETING CONTINUATION	$306,247
														Subtotal = $306,247

Issue Date FY: 2023 ( Subtotal = $202,375 )
2023	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Cancer Treatment Research	000	5	8/25/2023	NON-COMPETING CONTINUATION	$202,375
														Subtotal = $202,375

Issue Date FY: 2022 ( Subtotal = $536,258 )
2022	2022	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Cancer Treatment Research	000	4	9/8/2022	NON-COMPETING CONTINUATION	$536,258
														Subtotal = $536,258

Issue Date FY: 2021 ( Subtotal = $490,586 )
2021	2021	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Cancer Treatment Research	000	3	8/25/2021	NON-COMPETING CONTINUATION	$490,586
														Subtotal = $490,586

Issue Date FY: 2020 ( Subtotal = $520,500 )
2020	2020	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Cancer Treatment Research	000	2	8/20/2020	NON-COMPETING CONTINUATION	$520,500
														Subtotal = $520,500

Issue Date FY: 2019 ( Subtotal = $495,216 )
2019	2019	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Cancer Treatment Research	000	1	8/16/2019	NEW	$495,216
														Subtotal = $495,216

Grand Total All Awards = $2,551,182

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Artemin overexpression in oral cancer pain and carcinogenesis

Award Number: R01CA228525

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2019

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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