title: 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.
authors.affiliation: Biología Molecular, Universidad Nacional de Río Cuarto, Ruta 36 Km 601, Río Cuarto, 5800, Córdoba, Argentina.
authors.forename: Renzo Emanuel
authors.initials: RE
authors.lastname: Vera
authors.affiliation: Biología Molecular, Universidad Nacional de Río Cuarto, Ruta 36 Km 601, Río Cuarto, 5800, Córdoba, Argentina.
authors.forename: María Julia
authors.initials: MJ
authors.lastname: Lamberti
authors.affiliation: Biología Molecular, Universidad Nacional de Río Cuarto, Ruta 36 Km 601, Río Cuarto, 5800, Córdoba, Argentina.
authors.forename: Viviana Alicia
authors.initials: VA
authors.lastname: Rivarola
authors.affiliation: Biología Molecular, Universidad Nacional de Río Cuarto, Ruta 36 Km 601, Río Cuarto, 5800, Córdoba, Argentina. belenrumie@gmail.com.
authors.forename: Natalia Belén
authors.initials: NB
authors.lastname: Rumie Vittar
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008545:Melanoma / Q000473:pathology / Q000628:therapy*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D018874:Spheroids, Cellular; D016896:Treatment Outcome; D059016:Tumor Microenvironment / Q000235:genetics*
chemical_list: D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species
keywords: Melanoma; Monolayer; Photodynamic therapy; Spheroids; Tumor microenvironment