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. This grant has been continuously funded since 1980 and has been funded through June 2016.
Funded by NIH-NCI
Skin cancer is the most common malignancy in the world. One out of three new cancers is a skin cancer. More than 1 million cases of non-melanoma skin cancer (NMSC) (basal cell carcinoma [BCC] and squamous cell cancers [SCC]) occur annually. While the incidence rates for non-melanoma skin cancers continue to rise, there continues to be a substantial impact on morbidity, health and health care costs.
The overall goal of this program project (PPG) is to employ novel technologies and develop new therapeutic strategies to eradicate intraepithelial neoplasias in the skin (i.e. actinic keratosis, squamous cell carcinoma in situ) and dramatically reduce the risk of squamous cell carcinoma of the skin.
To achieve this goal, we will conduct a multilevel program of rational drug development, including: 1) the identification of the critical molecular targets in solar radiation signaling pathways for the development of SCC; 2) the selection of novel chemopreventive agents and synthesis of prodrugs that specifically “hit” these molecular targets in SCC and definitively interrupt their signaling pathways; 3) the testing of the most promising target-specific agents and prodrugs in preclinical pharmacology and toxicology models required for Investigational New Drug (IND) registrations; and 4) to conduct phase 0, I, IIa and IIb cancer prevention clinical trials of new IND-registered agents to prove target validity, chemopreventive safety, tolerability and efficacy.
Knowledge of the key molecular targets in solar ultraviolet radiation signal transduction pathways and the development of multiple topically administered agents that can hit and eradicate these targets ultimately will allow for personalized medical approaches to SCC chemoprevention. A major theme of this PPG fits the scheme of Discovery Development and Delivery. While the two basic science projects continue the aims of identification (discovery) of UV signaling target pathways and agents that modulate these targets, the clinical project will undertake the development process of moving the agents showing efficacy in the SCC mouse models into phase 0, 1, 2a and 2b human clinical trials. The delivery step occurs after agents demonstrate efficacy in phase 2b clinical trials. While this PPG will not take on the task of delivery by running phase III clinical trials, progress of earlier agents discovered and developed previously by the investigators involved in the proposed PPG have resulted in their commercialization, including Melanotan (a superpotent alpha-melanocyte stimulating hormone) now licensed to the company Clinuvel and myristyl nicotinate (MN) licensed to the company Niadyne.
This highly integrated program project, emphasizing a multidisciplinary, personalized medicine approach to the chemoprevention of squamous cell carcinoma of the skin can serve as a model for the chemoprevention of other common epithelial malignancies (e.g. lung and head and neck squamous cell cancers).
Project 1: G. Timothy Bowden, Project Leader. Targeting of mTOR Activity for Chemoprevention of Solar Light Induced Skin Cancer
Project 2: Zigang Dong, Project Leader. Targeting RSK2 and JNK2 Pathways for Chemoprevention of Solar Light Induced Skin Cancer
Project 3: Clara Curiel, Project Leaders. Translational Studies and Clinical Pharmacology of New Drugs for Chemoprevention of Skin Cancer
If you are interested in participating in or learning more about open clinical trials, please call 321-7745.
Core A - Administration: David S. Alberts and G. Timothy Bowden, Core Directors.
Core B - Biometry: Chengcheng Hu, Core Director
Core C - Biomarkers: Janine Einspahr, Core Director
Core D - Drug Development: Paul Myrdal, Core Director
Investigators - Organization
- Alberts, David S. (MD) - The University of Arizona, Arizona Cancer Center
- Bartels, Peter (PhD) - The University of Arizona, College of Optical Sciences
- Barton, Jennifer (PhD) - The University of Arizona, Biomedical Engineering
- Bode, Ann (PhD) - University of Minnesota, Hormel Institute
- Bowden, G. Timothy (PhD) - The University of Arizona, Cell Biology and Anatomy
- 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
- Dong, Zigang (DrPH) - University of Minnesota, Hormel Institute
- Einspahr, Janine (PhD) - The University of Arizona, College of Medicine
- Harris, Robin (PhD, MPH) - The University of Arizona, College of Public Health, Epidemiology
- Hu, Chengcheng (PhD) - The University of Arizona, College of Public Health, Biometry
- Krouse, Robert (MD) - The University of Arizona, Southern Arizona VA Medical Center
- Liotta, Lance (MD, PhD) - George Mason University, Department of Molecular and Microbiology
- Myrdal, Paul (PhD) - The University of Arizona, Pharmacy Practice and Science
- Petricoin, Emanuel (PhD) - George Mason University, Department of Molecular and Microbiology
- Prasad, Anil (MD) - The University of Arizona, Pathology
- Sagerman, Paul (MD) - The University of Arizona, College of Medicine, Dermatopathology
- Sligh, James (MD, PhD) - The University of Arizona, College of Medicine, Dermatology
- Warneke, James (MD) - The University of Arizona, College of Medicine
- Zhang, Jian (PhD) - The University of Arizona, Arizona Cancer Center
Collaborators and Consultants
Name - Organization
- DiGiovanni, John (PhD) - MD Anderson, Science Park, Department of Carcinogenesis
- Mash, Eugene (PhD) - The University of Arizona, Department of Chemistry
- Sanford, Philip (PhD) - The University of Arizona, Bio5 Institute
- Seligmann, Bruce (MD, PhD) - High Throughput Genomics
- Watts, George (PhD) - The University of Arizona, Arizona Cancer Center