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

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.