Efficiently Photocontrollable or Not? Biological Activity of Photoisomerizable Diarylethenes

Photodynamic therapy (PDT) is a clinically approved cancer therapy, based on a photochemical reaction between a light activatable molecule or photosensitizer, light, and molecular oxygen. When these three harmless components are present together, reactive oxygen species are formed. These can directly damage cells and/or vasculature, and induce inflammatory and immune responses. PDT is a two-stage procedure, which starts with photosensitizer administration followed by a locally directed light exposure, with the aim of confined tumor destruction. Since its regulatory approval, over 30 years ago, PDT has been the subject of numerous studies and has proven to be an effective form of cancer therapy. This review provides an overview of the clinical trials conducted over the last 10 years, illustrating how PDT is applied in the clinic today. Furthermore, examples from ongoing clinical trials and the most recent preclinical studies are presented, to show the directions, in which PDT is headed, in the near and distant future. Despite the clinical success reported, PDT is still currently underutilized in the clinic. We also discuss the factors that hamper the exploration of this effective therapy and what should be changed to render it a more effective and more widely available option for patients.