The development of novel approaches to the treatment of non-melanoma skin cancer is of significance. Non-melanotic skin cancers are by far the most prevalent malignancy in the US, comprising about half of all other cancers combined. Basal cell carcinomas (BCCs) are the overwhelming majority of skin malignancies. Our experience and that of others shows that ALA-PDT can have efficacy comparable to ordinary surgery and is advantageous in the skin because it provides enhanced selectivity, outstanding cosmesis, and the option of treating multiple lesions and large surface areas, particularly for nevoid BCC syndrome (NBCCS) patients or those with complex or multiple lesions. However it has reduced overall efficacy, can be painful and relatively ineffective for thick lesions. Therefore the overall goal of this project is to understand the underlying mechanisms in order to improve the efficacy of ALA-PDT, without compromising its selectivity and cosmetic benefits. In the current funding period we have shown, that recurrence basal cell carcinoma (BCC) can be minimized by high light doses at high irradiances, and that PDT treatment efficiency can be greatly improved and pain virtually eliminated at low irradiances. This has led to the hypothesis that elucidation of the low irradiance fluence-tumor response relationship is critical for optimizing efficacy of PDT. PDT can be compromised by vasospasm that locally limits oxygenation, and by inhomogeneous distributions of photosensitizer within the tumor. We hypothesize that examination of perfusion and intra-tumor vascular and photosensitizer distributions is critical for choosing appropriate treatment strategies, understanding mechanisms and constructing computational models for PDT. In collaboration with Project III, we have demonstrated for the first time that PDT enhances patient immune reactivity to a BCC-associated tumor antigen. Pre-clinical studies in Project III have shown that PDT enhanced anti-tumor immunity can be further augmented by addition of an immune modulating agent. We hypothesize that ALA-PDT induced immune responses improve clinical outcomes and can be augmented by the addition of immune modulators, and that vaccination with PDT-treated cells will treat existing BCC and prevent new carcinomas. Finally, we have shown that PDT efficacy can be improved in pre-clinical models through the addition of agents that potentiate effects of oxidative intracellular damage and inhibit tumor growth. We hypothesize that these agents will also improve clinical outcomes with topical and systemic photosensitizers.

Public Health Relevance

Clinical PDT has developed with little attention to, or understanding of the effects of treatment parameters on selectivity and outcomes. We have shown the fundamental importance of irradiance on both selectivity and outcome, and also on host responses. Work in the last funding period has discovered real-time metrics that can be used to select appropriate treatment parameters. The information derived from the proposed work will not only benefit skin cancer, but also may lead to paradigm shifts in the approach to clinical PDT.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-GRB-P)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Roswell Park Cancer Institute Corp
United States
Zip Code
Baran, Timothy M; Foster, Thomas H (2014) Comparison of flat cleaved and cylindrical diffusing fibers as treatment sources for interstitial photodynamic therapy. Med Phys 41:022701
Lai, Jinhuo; Cai, Qian; Biel, Merrill A et al. (2014) Id1 and NF-?B promote the generation of CD133+ and BMI-1+ keratinocytes and the growth of xenograft tumors in mice. Int J Oncol 44:1481-9
Rohrbach, Daniel J; Muffoletto, Daniel; Huihui, Jonathan et al. (2014) Preoperative mapping of nonmelanoma skin cancer using spatial frequency domain and ultrasound imaging. Acad Radiol 21:263-70
Rigual, Nestor; Shafirstein, Gal; Cooper, Michele T et al. (2013) Photodynamic therapy with 3-(1'-hexyloxyethyl) pyropheophorbide a for cancer of the oral cavity. Clin Cancer Res 19:6605-13
James, Nadine S; Chen, Yihui; Joshi, Penny et al. (2013) Evaluation of polymethine dyes as potential probes for near infrared fluorescence imaging of tumors: part - 1. Theranostics 3:692-702
Zeitouni, Nathalie C; Paquette, Anne D; Housel, Joseph P et al. (2013) A retrospective review of pain control by a two-step irradiance schedule during topical ALA-photodynamic therapy of non-melanoma skin cancer. Lasers Surg Med 45:89-94
Mitra, Soumya; Modi, Kshitij D; Foster, Thomas H (2013) Enzyme-activatable imaging probe reveals enhanced neutrophil elastase activity in tumors following photodynamic therapy. J Biomed Opt 18:101314
Ethirajan, Manivannan; Chen, Ping; Ohulchanskyy, Tymish Y et al. (2013) Regioselective synthesis and photophysical and electrochemical studies of 20-substituted cyanine dye-purpurinimide conjugates: incorporation of Ni(II) into the conjugate enhances its tumor-uptake and fluorescence-imaging ability. Chemistry 19:6670-84
Rigual, Nestor R; Shafirstein, Gal; Frustino, Jennifer et al. (2013) Adjuvant intraoperative photodynamic therapy in head and neck cancer. JAMA Otolaryngol Head Neck Surg 139:706-11
Brackett, Craig M; Muhitch, Jason B; Evans, Sharon S et al. (2013) IL-17 promotes neutrophil entry into tumor-draining lymph nodes following induction of sterile inflammation. J Immunol 191:4348-57

Showing the most recent 10 out of 131 publications