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Targeted Prevention for Non-Melanoma Skin Cancer

Award Number: P01CA229112
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/10/2019
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Targeted Prevention for Non-Melanoma Skin Cancer - ABSTRACT Overall Targeted Prevention for Non-Melanoma Skin Cancer Skin cancer is the most common malignancy worldwide. One out of three new cancers is a skin cancer. Approximately 5 million cases of non-melanoma skin cancer (NMSC) – basal cell carcinoma (BCC) and cutaneous squamous cell carcinomas (cSCC) occur annually. Incidence rates for NMSC continue to rise, creating a substantial impact on morbidity and health care costs that account for $8.1 billion/year for skin cancer treatment. The majority of these lesions represent keratinocytic neoplasms. The overall goal of this multi- institutional Program Project Grant (PPG) is to employ novel technologies and develop new targeted prevention strategies to eradicate intraepithelial neoplasias in the skin (e.g. actinic keratosis, squamous cell carcinoma in situ), and thereby, to dramatically reduce the risk of cSCC. To achieve this goal, we will conduct a multilevel program of rational drug development, including: 1) to assess, in experimental models and human studies, the significance of TLR4 and TOPK/PRPK signaling pathways in skin carcinogenesis leading to cSCC development; 2) to evaluate the relationship between TLR4 and TOPK/PRPK activation and previously established signaling pathways of relevance in AK and cSCC development; 3) to identify and develop novel therapeutic preventive agents that specifically “hit” these molecular targets in cSCC mouse models and effectively modulate their signaling pathways; 4) to test the most promising target-specific agents in preclinical pharmacology models; and 5) to assess target engagement and safety of selected agents through pilot and Phase 1 clinical trials. Knowledge of the key molecular targets in solar ultraviolet (UV) radiation signaling pathways and the development of multiple topically administered agents that can hit and effectively modulate these targets ultimately will allow for precision medicine based approaches in cSCC prevention. While the two basic science projects (Projects 1 and 2) aim to identify and validate UV-induced signaling pathways and agents that modulate these targets, the clinical project (Project 3) will undertake the task of moving leading candidate drugs from mouse models into acute solar simulated light studies and Phase 1 clinical trials. Novel technologies include signaling network analysis using state-of-the-art proteomic arrays coupled with the latest exploratory and downstream bioinformatic approaches and in vivo reflectance confocal microscopy for non-invasive assessment and selection of tissue samples in human skin. This highly integrated and translational research based program project, emphasizing a multidisciplinary, precision medicine approach for the prevention of cSCC of the skin can also serve as a model for preventing other epithelial malignancies.


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: 2024 ( Subtotal = $0 )
2024	2023	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Cancer Cause and Prevention Research	000	5	5/3/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $1,301,234 )
2023	2023	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Cancer Cause and Prevention Research	001	5	9/1/2023	NON-COMPETING CONTINUATION	$1,301,234
2023	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cancer Cause and Prevention Research	000	4	1/31/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,301,234

Issue Date FY: 2022 ( Subtotal = $1,593,830 )
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cancer Cause and Prevention Research	001	4	8/18/2022	NON-COMPETING CONTINUATION	$1,359,369
2022	2022	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cancer Cause and Prevention Research	000	3	6/14/2022	SUPPLEMENT FOR EXPANSION	$234,461
2022	2021	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cancer Cause and Prevention Research	002	3	9/9/2022	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $1,593,830

Issue Date FY: 2021 ( Subtotal = $1,449,317 )
2021	2021	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cancer Cause and Prevention Research	000	3	8/25/2021	NON-COMPETING CONTINUATION	$1,383,249
2021	2021	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cancer Cause and Prevention Research	001	3	8/26/2021	SUPPLEMENT FOR EXPANSION	$66,068
														Subtotal = $1,449,317

Issue Date FY: 2020 ( Subtotal = $1,408,862 )
2020	2020	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cancer Cause and Prevention Research	001	2	9/17/2020	SUPPLEMENT FOR EXPANSION	$33,928
2020	2020	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cancer Cause and Prevention Research	000	2	9/3/2020	NON-COMPETING CONTINUATION	$1,374,934
														Subtotal = $1,408,862

Issue Date FY: 2019 ( Subtotal = $1,392,093 )
2019	2019	UNIVERSITY OF ARIZONA	888 N EUCLID AVE RM 510	TUCSON	AZ	85719	PIMA	USA	Cancer Cause and Prevention Research	000	1	9/10/2019	NEW	$1,392,093
														Subtotal = $1,392,093

Grand Total All Awards = $7,145,336

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Targeted Prevention for Non-Melanoma Skin Cancer

Award Number: P01CA229112

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/10/2019

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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