Photodynamic Therapy of Skin Cancers: A New Therapeutic Alternative?

Abstract

A photodynamic reaction is the excitation of a photosensitizer, mainly porphyrin derivatives, by visible light emitted by lamps or lasers in the presence of oxygen resulting in the generation of reactive oxygen species (ROS), in particular singlet oxygen. These ROS mediate cellular, e.g. lipid peroxidation, and vascular effects, e.g. thrombosis, depending on the tissue localization of the photosensitizer. The result is a direct or indirect cytotoxic effect on the target cells. Photodynamic therapy is a treatment modality which has been mainly shown to be effective for precancerous and cancerous conditions like actinic keratosis, Bowen’s disease, initial squamous cell carcinoma and basal cell carcinoma. The main research topic over the last decade has been the synthesis and experimental evaluation of chemically pure photosensitizers, which generate a high quantum yield of singlet-oxygen, high selectivity for the diseased tissue and exhibit limited photosensitivity, when administered systemically. However, for dermatologic indications the use of photosensitizers which can be applied topically is of particular interest. Moreover, to facilitate introduction into dermatologic private practice there is also a need for cheap and reliable light sources. Therefore recent work has been focused on the development and evaluation of topical photosensitizers (like the heme precursor 5- aminolevulinic acid inducing photosensitizing porphyrins) and incoherent light sources (lamps). Cure rates reported for very superficial lesions (<2 mm) are close to that of other therapeutic modalities. However, PDT is still in its experimental state and there is need for comparative phase III-studies and standardized therapeutic protocols to define the place of photodynamic therapy in the treatment of skin cancers.