Projects per year
Project Details
Description
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.
Status | Active |
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Effective start/end date | 9/10/19 → 8/31/24 |
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Projects
- 2 Finished
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Project 2: TOPK/PRPK as Novel Targets for Skin Cancer Prevention
Morris, R. J. & Morris, R. R. J.
4/1/19 → 8/31/23
Project: Research project
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