Photodynamic therapy: A systems biology approach

Photodynamic therapy (PDT) is a rapidly advancing treatment for multiple diseases. PDT involves the administration of a nontoxic drug or dye known as a photosensitizer (PS), either systemically, locally, or topically, to a patient bearing a lesion (frequently but not always cancer), followed after some time by the illumination of the lesion with visible light; in the presence of oxygen, leads to the generation of cytotoxic species and consequently to cell death and tissue destruction. The light is absorbed by the PS molecule and the excited state PS transfers energy to ground state molecular oxygen, forming a reactive oxygen species that oxidize lipids, proteins, and nucleic acids. The resulting damage to essential biomolecules kills target cells by necrosis, apoptosis, or autophagy. When used as a cancer treatment PDT is known to cause direct tumor cell killing, severe damage to tumor blood vessels, and also produce an acute inflammatory reaction that can stimulate the immune system to recognize, track down, and even kill distant tumor cells that could cause metastases. This chapter focuses on studies of PDT that have employed a systems biology approach. These experiments have been frequently carried out using gene-expression micro-arrays. We will cover protective responses induced by PDT that include activation of transcription factors, heat shock proteins, antioxidant enzymes, and antiapoptotic pathways. Elucidation of these mechanisms might result in the design of more effective combination strategies to improve the antitumor efficacy of PDT. Specific pathways shown to be activated after PDT are heat shock proteins 90, 70, and 27, heme oxygenase, and cyclooxygenase-2.