Photodynamic therapy (
PDT) is a cytotoxic treatment, which can induce cells to initiate a rescue response, or to undergo cell death, either apoptosis or
necrosis. The many signaling pathways involved in these processes are the topic of this review. The subcellular localization of the
photosensitizer has been shown to be a key factor in the outcome of
PDT. Mitochondrial localized
photosensitizers are able to induce apoptosis very rapidly. Lysosomal localized
photosensitizers can elicit either a necrotic or an apoptotic response. In the plasma membrane, a target for various
photosensitizers, rescue responses, apoptosis and
necrosis is initiated. Several
protein phosphorylation cascades are involved in the regulation of the response to
PDT. Finally, a number of stress-induced
proteins play a role in the rescue response after
PDT. Notably, the induction of apoptosis by
PDT might not be crucial for an optimal outcome. Recent studies indicate that abrogation of the apoptotic pathway does alter the clonogenic survival of the cells after
PDT. Further studies, both in vitro and especially in vivo could lead to more efficient combination
therapies in which signaling pathways, involved in cell death or rescue, are either up- or downregulated before
PDT.