Ready player one? Autophagy shapes resistance to photodynamic therapy in cancers

Photodynamic therapy (PDT) is a procedure used in cancer therapy that has been shown to be useful for certain indications. Considerable evidence suggests that PDT might be superior to conventional modalities for some indications. In this report, we examine the relationship between PDT responsiveness and autophagy, which can exert a cytoprotective effect. Autophagy is an essential physiological process that maintains cellular homeostasis by degrading dysfunctional or impaired cellular components and organelles via a lysosome-based pathway. Autophagy, which includes macroautophagy and microautophagy, can be a factor that decreases or abolishes responses to various therapeutic protocols. We systematically discuss the mechanisms underlying cell-fate decisions elicited by PDT; analyse the principles of PDT-induced autophagy, macroautophagy and microautophagy; and present evidence to support the notion that autophagy is a critical mechanism in resistance to PDT. A combined strategy involving autophagy inhibitors may be able to further enhance PDT efficacy. Finally, we provide suggestions for future studies, note where our understanding of the relevant molecular regulators is deficient, and discuss the correlations among PDT-induced resistance and autophagy, especially microautophagy.