Mechanisms of Resistance to Photodynamic Therapy: An Update

Abstract

Photodynamic Therapy (PDT) involves the combination of light andphotosensitizer (PS). Therefore, it is possible for cells to develop resistance basedon the doses of PS used or the light dose. The data compiled by several authorsmake it clear that the degree of cell resistance to PDT is highly dependent on the PSused; however, no cellular characteristics have yet been identified as predictors ofPDT resistance. The mechanisms by which the treated tissue becomes resistant tothe PS share some similarities to those found in general drug resistance and radioresistance,and they are mainly related to both the bioavailability of the PS and tothe mechanisms of detoxification of the generated reactive oxygen species. Amongthe features related to PDT resistance are: the expression of p-glycoprotein andABCG2 transporters, the abrogation of apoptosis and autophagy, the induction ofantioxidant defences, the induction of HSPs changes in cytoskeleton and adhesion,the induction of cyclooxygenases, the production of nitric oxide and hypoxia; theseare some but not all of the factors involved in the development of resistance. As ageneral rule, all the authors that reported resistance to PDT have attributed this phenomenonto several factors acting in concert. In this chapter, we will review someof the most important aspects related to PDT resistance.