23 February 2009 Enhancement and optimization of PpIX-based photodynamic therapy of skin cancer: translational studies from bench to clinic
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Abstract
Nonmelanoma skin carcinomas are the most common of all human cancers. Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) has been used to treat these tumors, but has shown variable results. We are pursuing a multifaceted approach toward optimizing tumor responsiveness. First, a new paradigm is being developed in which tumors are pretreated with differentiation-inducing agents, e.g. methotrexate or Vitamin D, to enhance synthesis of protoporphyrin IX (PpIX) and improve tumor cell killing upon exposure to 635 nm light. This principle was first elucidated in cell culture studies, and has now been shown to hold true for murine skin tumors, and for a human subcutaneous tumor model (A431 cells injected in nude mice). Clinical trials to test methotrexate and Vitamin D as augmenting agents for ALA-PDT of nonmelanoma skin cancer are being designed. Second, better methods to measure PpIX in patients' skin tumors in real time are being developed. In a clinical study to measure PpIX in patients with dysplastic skin lesions, in vivo fluorescence dosimetry was used to measure the accumulation of PpIX over time, and revealed that intralesional PpIX may reach clinically-useful levels earlier than previously thought for the treatment of actinic keratoses. In a second clinical study to examine depth of PpIX production in nonmelanoma skin cancer, the depth of PpIX within BCC tumors was found at relatively deep levels (>1 mm) in some tumor nests, but not in others. Production of PpIX in deep squamous cell carcinoma was very low. In summary, molecular approaches such as differentiation therapy to enhance ALA-PDT for individual patients may ultimately be needed to help to improve skin cancer responses to this modality.
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Edward V. Maytin, Edward V. Maytin, Sanjay Anand, Sanjay Anand, Christine Baran, Christine Baran, Golara Honari, Golara Honari, Sara Lohser, Sara Lohser, Angela Kyei, Angela Kyei, Philip Bailin, Philip Bailin, Brian W. Pogue, Brian W. Pogue, } "Enhancement and optimization of PpIX-based photodynamic therapy of skin cancer: translational studies from bench to clinic", Proc. SPIE 7164, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XVIII, 71640K (23 February 2009); doi: 10.1117/12.808174; https://doi.org/10.1117/12.808174
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