Photodynamic Therapy in Melanoma - Where do we Stand?

Background: Malignant melanoma is one of the most aggressive malignant tumors, with unpredictable evolution. Despite numerous therapeutic options, like chemotherapy, BRAF inhibitors and immunotherapy, advanced melanoma prognosis remains severe. Photodynamic therapy (PDT) has been successfully used as the first line or palliative therapy for the treatment of lung, esophageal, bladder, non melanoma skin and head and neck cancers. However, classical PDT has shown some drawbacks that limit its clinical application in melanoma. Objective: The most important challenge is to overcome melanoma resistance, due to melanosomal trapping, presence of melanin, enhanced oxidative stress defense, defects in the apoptotic pathways, immune evasion, neoangiogenesis stimulation. Method: In this review we considered: (1) main signaling molecular pathways deregulated in melanoma as potential targets for personalized therapy, including PDT, (2) results of the clinical studies regarding PDT of melanoma, especially advanced metastatic stage, (3) progresses made in the design of anti-melanoma photosensitizers (4) inhibition of tumor neoangiogenesis, as well as (5) advantages of the derived therapies like photothermal therapy, sonodynamic therapy. Results: PDT represents a promising alternative palliative treatment for advanced melanoma patients, mainly due to its minimal invasive character and low side effects. Efficient melanoma PDT requires: (1) improved, tumor targeted, NIR absorbing photosensitizers, capable of inducing high amounts of different ROS inside tumor and vasculature cells, possibly allowing a theranostic approach; (2) an efficient adjuvant immune therapy. Conclusion: Combination of PDT with immune stimulation might be the key to overcome the melanoma resistance and to obtain better, sustainable clinical results.