4-thiothymidine sensitization of DNA to UVA offers potential for a novel photochemotherapy

Photochemotherapy, in which ultraviolet radiation (UVR: 280–400 nm) or visible light is combined with a photosensitizing drug to produce a therapeutic effect that neither drug or radiation can achieve alone, is a proven therapeutic strategy for a number of non-malignant hyperproliferative skin conditions and various cancers. Examples are psoralen plus UVA (320–400 nm) radiation (PUVA) and photodynamic therapy (PDT). All existing photochemotherapies have drawbacks–for example the association of PUVA with the development of skin cancer, and pain that is often associated with PDT treatment of skin lesions. There is a clear need to develop alternative approaches that involve lower radiation doses and/or improved selectivity for target cells. In this review, we explore the possibility to address this need by exploiting thionucleoside-mediated DNA photosensitisation to low, non toxic doses of UVA radiation.