Project 1: Small Molecule Enhancers of Photodynamic Therapy for Skin Cancer
Project Leader: Edward Maytin, MD PhD

Project 1 will establish clinical efficacy through phase I and II studies of combination therapies using small molecules, e.g., 5-FU and Vitamin D, that sensitize the tumor to effective ALA-based PDT for human non-melanoma skin cancer.

Non-melanoma skin cancer, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), are the most common of all cancers. Together these cancers affect over 3,000,000 people in the U.S., and are the fifth most expensive group of cancers to treat in both the U.S. and Europe.1,2

Project 1 will focus on two areas of NMSC management:

1. Treatment and prevention of frequent and aggressive squamous cell carcinoma, a serious problem in organ transplant patients
2. The use of PDT to treat basal cell carcinoma

PDT offers unique advantages over surgery or ionizing radiation for the treatment of non-melanoma skin cancers. ALA-PDT is a scar-free treatment modality that can be repeated indefinitely without mutagenic risk. Project 1 utilizes ALA-PDT in combination with one or more of proposed adjuvantive treatments, and provides new options for patients and physicians who treat non-melanoma skin cancer.

Project 1 has identified 5-FU as an enhancer of cellular differentiation, and discovered a new potential mechanism where upregulation of the p53 oncogene may underlie the effect of 5-FU. In subcutaneous A431 mice, pretreatment with 5-FU leads to elevated p53 levels in the tumor tissue in vivo (Figure 1A), which correlates closely with apoptosis after ALA-PDT (Figure 1B).

1Housman, Feldman, Williford, Fleischer, Goldman, Acostamadiedo & Chen. Skin cancer is among the most costly of all cancers to treat for the Medicare population. J Am Acad Dermatol 48, 425-429 (2003).
2Cakir, Admason & Cingi. Epidemiolgoy and economic burden of nonmelanoma skin cancer. Facial Plast Surg Clin North Am 20, 419-422 (2012).