Wednesday, December 24, 2025 12/24/2025

TRPV1 nociceptors in oral carcinogenesis and pain

Award Number: R01CA231396
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2027

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TRPV1 nociceptors in oral carcinogenesis and pain - Project Summary Oral cancer pain is more severe than all other cancers. Patients with metastatic oral cancer experience the greatest pain. Oral cancers activate neurons and produce pain; however, the effect of nociceptors on oral cancer is largely unknown. The mechanisms of reciprocal interaction between oral cancer and neurons, and how the interactions promote cancer and pain, are not known. The long-term goal is to improve management of oral cancer patients and obviate opioids by identifying components of the cancer microenvironment that are viable targets to treat cancer and oral cancer pain. The overall objectives for this application are to (i) elucidate the phenotype and distribution of transient receptor potential channel, vanilloid subfamily member (TRPV1) + neurons innervating painful and metastatic oral cancers, (ii) measure sensitization and activation of TRPV1+ neurons by mediators secreted by oral cancer, and (iii) determine the contribution of TRPV1+ neurons to oral carcinogenesis. The central hypothesis is that oral cancers release mediators, including mediators carried in extracellular vesicles (EVs) that sensitize and activate nociceptors inducing oral cancer pain. The cancer- primed nociceptors, in turn, promote cancer. The rationale for the project is that identification of components of the cancer-nerve interaction provides the opportunity to develop approaches to treat oral cancer and oral cancer pain, thereby reducing use of opioids. The central hypothesis will be tested by pursuing three specific aims: 1) Determine the type and density of innervation in oral cancers in relation to pain and metastasis; 2) Investigate sensitization of trigeminal (TG) neurons by cancer pain mediators; and, 3) Investigate cancer promotion by cancer activated and sensitized TRPV1+ neurons and evaluate the potential to stop cancer and alleviate cancer pain by antagonizing signaling via the sensory neuropeptide, calcitonin gene related peptide (CGRP). Under the first aim, neuronal innervation of the cancer will be evaluated in a retrospective patient cohort with known pain and nodal status, and testing for capsaicin (TRPV1 agonist) sensitivity and measurement of pain will be performed in prospectively enrolled oral cancer patients. For the second aim, a gene associated with pain and metastasis and miRNAs from EVs will be investigated as pain mediators. For the third aim a mouse oral carcinogenesis model will be used to investigate the impact of TRPV1 abundance on cancer incidence and phenotype, the impact of CGRP signaling on cancer promotion, and the potential for CGRP/CGRP receptor therapies for treating and preventing oral cancer and oral cancer pain. The research proposed is innovative because it is based on two new findings regarding oral cancer pain: (1) newly identified putative cancer pain mediators overexpressed in metastatic cancers from patients reporting high levels of pain, and (2) involvement of EVs in cancer induced nociceptive behavior. The proposed research is significant because these studies will lay the foundation for clinical trials to assess CGRP and CGRP receptor targeted therapies, which are FDA-approved for migraine, to treat cancer and attenuate cancer pain.


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	2025	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Cancer Biology Research	000	5	12/2/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $615,159 )
2025	2025	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Cancer Biology Research	000	5	6/6/2025	NON-COMPETING CONTINUATION	$615,159
														Subtotal = $615,159

Issue Date FY: 2024 ( Subtotal = $596,271 )
2024	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Cancer Biology Research	000	4	2/28/2024	NON-COMPETING CONTINUATION	$564,889
2024	2024	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Cancer Biology Research	001	4	4/18/2024	NON-COMPETING CONTINUATION	$31,382
														Subtotal = $596,271

Issue Date FY: 2023 ( Subtotal = $605,687 )
2023	2023	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Cancer Biology Research	000	3	3/1/2023	NON-COMPETING CONTINUATION	$605,687
														Subtotal = $605,687

Issue Date FY: 2022 ( Subtotal = $627,398 )
2022	2022	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Cancer Biology Research	000	2	4/1/2022	NON-COMPETING CONTINUATION	$627,398
														Subtotal = $627,398

Issue Date FY: 2021 ( Subtotal = $625,751 )
2021	2021	NEW YORK UNIVERSITY	70 WASHINGTON SQ S	NEW YORK	NY	10012	NEW YORK	USA	Cancer Biology Research	000	1	2/23/2021	NEW	$625,751
														Subtotal = $625,751

Grand Total All Awards = $3,070,266

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TRPV1 nociceptors in oral carcinogenesis and pain

Award Number: R01CA231396

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/01/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2027

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