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Updated: Apr 1, 2026
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Developing strategies to predict photodynamic therapy outcome: the role of melanoma microenvironment
Renzo Emanuel Vera1, María Julia Lamberti1, Viviana Alicia Rivarola1
1Biología Molecular, Universidad Nacional de Río Cuarto, Ruta 36 Km 601, Río Cuarto, 5800, Córdoba, Argentina.
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.
Insights
Photodynamic therapy (PDT) shows promise for melanoma treatment. New preclinical models are needed to bridge the gap between lab findings and clinical results for effective melanoma therapy.
Area of Science:
- Oncology
- Biomedical Engineering
Background:
- Melanoma is an aggressive skin cancer with limited treatment options.
- Photodynamic therapy (PDT) uses photosensitizers and light to generate reactive oxygen species for antitumor effects.
Purpose of the Study:
- To review existing data on photodynamic therapy for melanoma.
- To identify limitations in current preclinical models for PDT research.
- To propose improved experimental platforms for melanoma treatment optimization.
Main Methods:
- Comparative analysis of in vitro, in vivo, and clinical studies on PDT for melanoma.
- Review of 3D culture systems and heterotypic cultures mimicking tumor architecture and microenvironment.
- Literature review of PDT strategies and their efficacy in melanoma models.
Main Results:
- A significant disconnection exists between in vitro hypotheses and in vivo/clinical outcomes for PDT in melanoma.
- Tumor microenvironment interactions are critical for melanoma resistance to therapy.
- 3D and heterotypic culture systems offer more realistic models of tumor biology.
Conclusions:
- Current preclinical models for PDT in melanoma require enhancement to better reflect tumor complexity.
- Development of advanced preclinical platforms is crucial for optimizing PDT clinical outcomes.
- Exploiting tumor-stromal interactions presents a novel therapeutic target for melanoma treatment.
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