Signaling pathways in cell death and survival after photodynamic therapy

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 th e topic of this review. The subcellular localization of the photosensitizer has been shown to be a key factor in the outcome of PDT. Mitochondrial loc alized photosensitizers are able to induce apoptosis very rapidly. Lysosoma l localized photosensitizers can elicit either a necrotic or an apoptotic r esponse. In the plasma membrane, a target for various photosensitizers, res cue responses, apoptosis and necrosis is initiated. Several protein phospho rylation cascades are involved in the regulation of the response to PDT. Fi nally, a number of stress-induced proteins play a role in the rescue respon se after PDT. Notably, the induction of apoptosis by PDT might not be cruci al for an optimal outcome. Recent studies indicate that abrogation of the a poptotic pathway does alter the clonogenic survival of the cells after PDT. Further studies, both in vitro and especially in vivo could lead to more e fficient combination therapies in which signaling pathways, involved in cel l death or rescue, are either up- or downregulated before PDT. (C) 2000 Els evier Science S.A. All rights reserved.