Photodynamic therapy of skin cancers: Sensitizers, clinical studies and future directives

Photodynamic therapy (PDT) is a new modality of skin cancer treatment, It i nvolves the administration of photosensitizing drugs which. when localized in tumor tissue can produce its destruction by absorbing an adequate dose o f light of an appropriate wavelength. A large number of photosensitizing ag ents have been tested in PDT experiments. Topical application of 5-aminolev ulinic acid (5-ALA) followed by light irradiation is the most commonly used method. 5-ALA is a prodrug converted in situ via the heme cycle into proto porphyrin IX. an effective photosensitizer agent. Treatment of nonmelanoma skin cancers by PDT has met with varying degrees of success. In the case of 5-ALA, this therapy's main limitation is the poor penetration of 5-ALA int o skin. due to hydrophilic and charge characteristics. However. the efficac y of 5-ALA-PDT may he improved by (a) development of adequate drug delivery systems: (b) use of enhancers of PpIX production and accumulation in targe t tissue, and (c) modifications of the 5-ALA molecule. Optimal timing. ligh t sources, doses. and number of applications are also important factors for topical 5-ALA therapy and must be well defined. The aim of this review is to highlight recent progress in 5-ALA-PDT of skin cancer, and to present wa ys holding promise for its improvement.