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

Abstract

Melanoma is among the most aggressive and treatment-resistant human skin cancer. Photodynamic therapy (PDT), a minimally invasive therapeutic modality, is a promising approach to treating melanoma. It combines a non-toxic photoactivatable drug called photosensitizer with harmless visible light to generate reactive oxygen species which mediate the antitumor effects. The aim of this review was to compile the available data about PDT on melanoma. Our comparative analysis revealed a disconnection between several hypotheses generated by in vitro therapeutic studies and in vivo and clinical assays. This fact led us to highlight new preclinical experimental platforms that mimic the complexity of tumor biology. The tumor and its stromal microenvironment have a dynamic and reciprocal interaction that plays a critical role in tumor resistance, and these interactions can be exploited for novel therapeutic targets. In this sense, we review two strategies used by photodynamic researchers: (a) developing 3D culture systems which mimic tumor architecture and (b) heterotypic cultures that resemble tumor microenvironment to favor therapeutic regimen design. After this comprehensive review of the literature, we suggest that new complementary preclinical models are required to better optimize the clinical outcome of PDT on skin melanoma.

Cancer cell spheroids are a better screen for the photodynamic efficiency of glycosylated photosensitizers

“…the physical-chemical conditions of oxygen, pH, and nutrient gradients. Some advantages of using spheroid cultures in PS screening are reported [1, 3, 4, 7–9, 17]; however, a high throughput screening that involves the use of different cancer cell lines is hampered by the difficulty of obtaining homogeneous spheroid cultures. The need to assay biochemical activity and viability of the spheroids for each culture is underappreciated.…”

“…PDT triggers cell death in cancer cells by formation of reactive oxygen species (ROS) generated by a photosensitizer (PS) when irradiated by light [1–9]. PDT can offer double selectivity via selective light irradiation such that areas not irradiated are unaffected [3], and the PS can be chemically modified to target specific tissues or environments, such as specific ligands on cancer cells or the low pH surrounding the milieu of a tumor [6]. Porphyrins are aromatic heterocyclic organic dyes that absorb intensely in the red region of the visible spectrum that is able to furthest penetrate tissue and skin.…”

A review and outlook in the treatment of osteosarcoma and other deep tumors with photodynamic therapy: from basic to deep

“…Although PDT has been studied on many malignancies for a long time, most researches have focused on superficial cancers, such as skin cancer [49], gastrointestinal cancers [50], head and neck cancers [51], and malignant melanomas [52]. Their location distinguishes these cancers from the tumors in deep tissue, such as glioma, pancreatic cancer, and OS, which suffer from the light deficiencies and surface tissue damage in PDT because of the coverage of muscles and skin.…”

Nanopartículas lipídicas sólidas e vesículas cataniônicas contendo ftalocianina de cloro alumínio aplicadas nos processos fotodinâmicos

“…melanócitos com atipia estrutural e arquitetural; (3) melanoma primário em fase de progressão radial: confinado à epiderme, crescendo lateralmente; (4) melanoma primário em fase de crescimento vertical: início da invasão da derme e aquisição de competência para a metástase e (5) melanoma metastático, preferencialmente em linfonodos, fígado, pulmão e cérebro (VERA et al, 2015;VILLANUEVA e HERLYN, 2008).…”

“…Assim, tratamentos alternativos para o melanoma maligno têm sido profundamente estudados para aumentar a chance de sobrevivência do paciente e cura da doença (AVCI et al, 2014;GIROTTI et al, 2014;KAWCZYK-KRUPKA et al, 2013;VERA et al, 2015).…”