Targeting Microenvironment of Melanoma and Head and Neck Cancers in Photodynamic Therapy
Ivana Ratkaj1, Martina Mušković1, Nela Malatesti1
1Department of Biotechnology, University of Rijeka, Rijeka, Croatia.
Background:
Photodynamic therapy (PDT), in comparison to other skin cancers, is still far less effective for melanoma, due to the strong absorbance and the role of melanin in cytoprotection. The tumour microenvironment (TME) has a significant role in tumour progression, and the hypoxic TME is one of the main reasons for melanoma progression to metastasis and its resistance to PDT. Hypoxia is also a feature of solid tumours in the head and neck region that indicates negative prognosis.
Objective:
The aim of this study was to individuate and describe systematically the main strategies in targeting the TME, especially hypoxia, in PDT against melanoma and head and neck cancers (HNC), and assess the current success in their application.
Methods:
PubMed was used for searching, in MEDLINE and other databases, for the most recent publications on PDT against melanoma and HNC in combination with the TME targeting and hypoxia.
Results:
In PDT for melanoma and HNC, it is very important to control hypoxia levels, and amongst the different approaches, oxygen self-supply systems are often applied. Vascular targeting is promising, but to improve it, optimal drug-light interval, and formulation to increase the accumulation of the photosensitiser in the tumour vasculature, have to be established. On the other side, the use of angiogenesis inhibitors, such as those interfering with VEGF signalling, is somewhat less successful than expected and needs to be further investigated.
Conclusion:
The combination of PDT with immunotherapy by using multifunctional nanoparticles continues to develop and seems to be the most promising for achieving a complete and lasting antitumour effect.
Insights
Photodynamic therapy (PDT) faces challenges in treating melanoma and head and neck cancers due to the tumor microenvironment (TME), particularly hypoxia. Combining PDT with immunotherapy using nanoparticles shows the most promise for effective cancer treatment.
Area of Science:
- Oncology
- Photochemistry
- Cancer Biology
Background:
- Photodynamic therapy (PDT) is less effective for melanoma compared to other skin cancers due to melanin's protective role and strong absorbance.
- Hypoxia within the tumor microenvironment (TME) significantly drives melanoma progression, metastasis, and resistance to PDT.
- Hypoxia in head and neck cancers (HNC) is a poor prognostic indicator.
Purpose of the Study:
- To systematically identify and describe strategies for targeting the TME, specifically hypoxia, in PDT for melanoma and HNC.
- To assess the current success and application of these TME-targeting strategies in PDT.
Main Methods:
- Systematic literature search of PubMed, MEDLINE, and other databases.
- Focus on recent publications concerning PDT for melanoma and HNC combined with TME targeting and hypoxia.
Main Results:
- Controlling hypoxia is crucial for PDT in melanoma and HNC; oxygen self-supply systems are frequently used.
- Vascular targeting strategies show promise but require optimization of drug-light intervals and photosensitizer formulations.
- Angiogenesis inhibitors targeting VEGF signaling have shown limited success and require further investigation.
Conclusions:
- Combining PDT with immunotherapy, particularly using multifunctional nanoparticles, is a developing and highly promising approach.
- This combination therapy holds potential for achieving complete and durable antitumor effects in melanoma and HNC.
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