Topical 4-thiothymidine is a viable photosensitiser for the photodynamic therapy of skin malignancies

Abstract

The nucleoside analogue 4-thiothymidine has shown great potential in vitro as a photosensitiser for the photodynamic therapy of numerous cancer cell lines. However, the limited penetrating power of UV-A radiation, to which it responds, raises doubts as to its practical usefulness in clinical applications. We addressed this issue by studying the penetration extent of topical thiothymidine and the antiproliferative effect of its combination with UV-A radiation on ex vivo basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) skin cancer biopsies, and normal skin. Our results show that both the intralesional concentration of the drug and the intensity of UV-A radiation are sufficient to activate the molecule and cause extensive death by apoptosis of the malignant cells. Normal skin biopsies were not significantly affected by the treatment.

Key words::

• 4-thiothymidine
• squamous cell carcinoma
• basal cell carcinoma
• photodynamic therapy

Acknowledgements

This work was funded by a research grant from Lokpal Ltd, London, UK, who has authorised publication of these data. The authors would like to thank Dr Peter Karran (CRUK) for helpful feedback and suggestions.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.