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
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,
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.