This Program Project Grant consists of two basic science projects, one clinical trial project, and four service cores. There are also two subcontracts with investigators at other institutions.
Funded by NIH-NCI
Targeted Prevention of 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 a 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.
Data Sharing Requests
- A description of the research to be performed using the requested data.
- A list of names and organizational affiliations of all those with whom the requester will engage in the research.
- A description of the means by which investigators will restrict access to confidential data.
Project 1: Sally Dickinson and Georg Wondrak. TLR4 as a Novel Target for Skin Cancer Prevention.
Project 2: Ann Bode and Eunmiri Roh. TOPK/PRPK as Novel Targets for Skin Cancer Prevention.
Project 3: Clara Curiel and Sherry Chow. Translational Studies and Clinical Pharmacology of TLR4 and TOPK Inhibitors for Prevention of Squamous Cell Carcinoma of the Skin.
If you are interested in participating in or learning more about open clinical trials, please call 321-7745.
Core A - Administration: Clara Curiel, Core Director.
Core B - Biostatistics and Bioinformatics: Chengcheng Hu and Denise Roe, Core Directors.
Core C – Molecular Targets: Clara Curiel and Sherry Chow, Core Directors.
Core D - Drug Development: Heidi Mansour, Core Director.
Investigators - Organization
- Billheimer, Dean (PhD) - The University of Arizona, College of Public Health, Epidemiology and Biostatistics
- Bode, Ann (PhD) - University of Minnesota, Hormel Institute
- Calvert, Valerie - George Mason University, Department of Molecular & Microbiology
- Chow, Sherry H. (PhD) - The University of Arizona, Pharmaceutical Sciences
- Curiel, Clara (MD) - The University of Arizona, College of Medicine, Dermatology
- Sally Dickinson (PhD) - The University of Arizona, College of Medicine, Cancer Biology and Pharmacology
- Hu, Chengcheng (PhD) - The University of Arizona, College of Public Health, Biometry
- Liotta, Lance (MD, PhD) - George Mason University, Department of Molecular and Microbiology
- Mansour, Heidi (PhD, RPh) - The University of Arizona, College of Pharmacy
- Petricoin, Emanuel (PhD) - George Mason University, Department of Molecular and Microbiology
- Roe, Denise (DrPH, MS) - The University of Arizona, College of Public Health, Biometry
- Roh, Eunmiri ((PhD) - University of Minnesota, Hormel Institute
- Schenten, Dominik (PhD) - The University of Arizona, College of Medicine, Immunobiology
- Warneke, James (MD) - The University of Arizona, College of Medicine
- Wondrak, Georg (PhD) - The University of Arizona, College of Pharmacy, Pharmacology and Toxicology