Photodynamic therapy in melanoma--an update

Melanoma, a cancer that arises from melanocytes is one of the most unresponsive cancers to known therapies. Several studies showed encouraging results of the efficacy of photodynamic therapy (PDT) using different experimental settings in vitro and in vivo as well as a few clinical reports, suggesting a possible role as an adjuvant therapy in the management of advanced melanoma (stage III and IV). In experimental settings, PDT using different protocols on human and mice melanoma cells induced significant apoptosis, necrosis, tumor growth arrest and prolonged the survival of the animals, but seldom achieved complete remission and/or was followed by recurrence and side effects. Clinical reports showed regression of choroidal melanoma and skin melanoma metastasis following PDT. PDT consists in administration of a photosensitizer, which undergoes excitation after suitable irradiation emitted from a light source and generates singlet oxygen (¹O₂) and other cytotoxic oxygen species such as superoxide anion radical (O₂·⁻) and hydroxyl radical (OH·). The antitumor effects result from the combination of direct tumor cell photodamage, destruction of tumor vasculature and activation of an immune response. To increase the effectiveness of PDT in melanoma, the therapy has to overcome the protective mechanisms like pigmentation and increased oxidative stress defense, possibly through inhibition of melanogenesis and melanosome targeted photosensitizers. The optimal protocols for tumor and vascular targeted PDT could destroy melanoma and endothelial tumor cells and activate the immune response, thus increasing the overall efficacy. Combination of PDT with immune stimulation therapies might increase the efficiency in destroying the initial tumor as well as micro metastases and decrease the melanoma relapses.