Abstract
Photodynamic Therapy (PDT) involves the combination of light and photosensitizer (PS). Therefore, it is possible for cells to develop resistance based on the doses of PS used or the light dose. The data compiled by several authors make it clear that the degree of cell resistance to PDT is highly dependent on the PS used; however, no cellular characteristics have yet been identified as predictors of PDT resistance. The mechanisms by which the treated tissue becomes resistant to the 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 to the mechanisms of detoxification of the generated reactive oxygen species. Among the features related to PDT resistance are: the expression of p-glycoprotein and ABCG2 transporters, the abrogation of apoptosis and autophagy, the induction of antioxidant defences, the induction of HSPs changes in cytoskeleton and adhesion, the induction of cyclooxygenases, the production of nitric oxide and hypoxia; these are some but not all of the factors involved in the development of resistance. As a general rule, all the authors that reported resistance to PDT have attributed this phenomenon to several factors acting in concert. In this chapter, we will review some of the most important aspects related to PDT resistance.
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