Melanoma resistance to photodynamic therapy: new insights

Abstract

Melanoma is the most dangerous form of skin cancer, with a steeply rising incidence and a poor prognosis in its advanced stages. Melanoma is highly resistant to traditional chemotherapy and radiotherapy, although modern targeted therapies such as BRAF inhibitors are showing some promise. Photodynamic therapy (PDT, the combination of photosensitizing dyes and visible light) has been tested for melanoma with some promising results, but melanoma is generally considered to also be resistant to PDT. Optical interference by the highly-pigmented melanin, the anti-oxidant effect of melanin, the sequestration of photosensitizers inside melanosomes, defects in apoptotic pathways, and the efflux of photosensitizers by ATP-binding cassette (ABC) transporters have all been implicated in melanoma resistance to PDT. Approaches to overcoming melanoma resistance to PDT include: the discovery of highly active photosensitizers absorbing in the 700-800-nm near infrared spectral region; interventions that can temporarily reduce the amount or the pigmentation of the melanin; compounds that can reverse apoptotic defects or inhibit drug-efflux of photosensitizers; and immunotherapy approaches that can take advantage of the ability of PDT to activate the host immune system to the treated tumor.

Developing strategies to predict photodynamic therapy outcome: the role of melanoma microenvironment

“…The PSs that absorb in near-infrared are much more suitable for PDT of melanoma because this region is most transparent to radiation and the tissues are deeply penetrated by photons; (2) melanin is considered an intracellular antioxidant, thus it neutralizes PDT-induced ROS and decreases PDT success; (3) melanosomes can act as drug trapping or sequestration agents; (4) members of the ATP-binding cassette (ABC) transporters are located in the plasmatic and melanosomal membrane and can reduce the effectiveness of treatment by lowering the concentration of the PSs inside the cell by expelling it into the extracellular space; (5) the depth of tumor infiltration prevents the homogeneous penetration of radiation remaining in areas that lack treatment [26].…”

Three-dimensional imaging and uptake of the anticancer drug combretastatin in cell spheroids and photoisomerization in gels with multiphoton excitation

“…Problems include optical interference by melanin pigmentation, melanin antioxidant properties, and apoptotic pathway defects. 43 To overcome this, photosensitizers that absorb in the NIR spectral region (700-800 nm) have been considered together with interventions for reducing melanin pigmentation and immunotherapy approaches. Although localized E → Z activation and toxicity of combretastatins could not be directly determined in spheroids at this stage, it was possible to demonstrate twophoton Z → E isomerization at depth within agarose gels.…”

Photosensitizers Imprinting Intracellular Signaling Pathways in Dermato-Oncology Therapy

“…PDT with verteporfin alone or in combination with bevacizumab may be useful as primary or preoperative procedure for ocular melanoma. There are also recent experimental studies involving amelanotic melanoma, the nonpigmented melanoma type owned to a poor differentiation of melanocytes, which produce less melanin, refractive to classic treatments and for which alternative therapies are taking into account [42]. Thus, in a mouse C57/BL6 model bearing B78H1 amelanotic melanoma, it was tested a novel PS assembly comprising a Zn(II)-phthalocyanine, a polyethylene glycol (PEG) derivative and gold nanoparticles.…”