As photodynamic therapy (PDT) becomes established as a treatment for cancer
, there is increasing interest in identifying critical mechanisms of cell k
illing and understanding the bases for effective photosensitizers. The exis
tence of multiple cellular targets makes it difficult to distinguish the cr
itical events leading to cell death from PDT. However, with more sensitive
techniques to detect photosensitizer localization, the isolation of PDT-res
istant and -sensitive mutants and the use of innovative molecular and bioch
emical strategies to map cellular events occurring during and after photose
nsitization, some order is emerging from the chaos. The subcellular localiz
ation of many photosensitizers and the early responses to light activation
indicate that mitochondria play a major role in photodynamic cell death. PD
T with many agents which damage or inhibit different or multiple mitochondr
ial targets has many of the desirable characteristics for an effective anti
-cancer therapy. (C) 2001 Elsevier Science B.V. All rights reserved.