[Frontiers in Bioscience 14, 4157-4172, January 1, 2009]

Molecular mechanisms of photodynamic therapy

Bernhard Ortel1, Christopher R. Shea1, Piergiacomo Calzavara-Pinton2

1Section of Dermatology, University of Chicago Medical Center, 5841 South Maryland Avenue, MC-5067, Chicago, IL 60637, 2 Department of Dermatology, University of Brescia, Piazzale Spedale Civile, I-25123 Brescia, Italy

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Molecular mechanisms 3.1. Molecular targeting 3.2. Molecular effects of photosensitization
3.2.1. Immediate effects
3.2.1.1. Photochemical reactions
3.2.1.2. Lipid peroxidation and protein crosslinks
3.2.2. Early molecular responses
3.2.2.1. Early response genes and transcriptional activation
3.2.2.2. Stress proteins
3.2.2.3. Signal transduction
3.2.2.4. Complement activation
3.2.2.5. Cytokines
3.2.3. Cell death after PDT
3.2.3.1. Apoptosis
3.2.3.1.1. Extrinisic pathway
3.2.3.1.2. Intrinsic pathway
3.2.3.2. Autophagy
3.2.3.3. Necrosis
3.2.4. Defensive responses
3.2.4.1. Vascular endothelial growth factor
3.2.4.2. Cyclooxygenase-2
3.2.4.3. Matrix metalloproteinases
3.2.4.4. Immunological responses
4. Perspective
5. Acknowledgment
6. References

1. ABSTRACT

Despite its more than 100-year history in experimental and clinical use, photodynamic therapy (PDT) is only starting to be appreciated for its full potential. PDT combines a photosensitizer (PS) and light in the presence of oxygen to treat cancer and other disorders. This manuscript reviews molecular mechanisms that have been evaluated over the past years for the effects of PDT at the cellular level as well as in therapeutic settings in vivo. The availability of multiple PS with different structures and functional properties makes PDT an extremely versatile and, conversely, a challenging approach to cancer therapy. The advancing understanding of molecular pathways helps to design improved regimens. As most cancers are being treated with combination therapies, PDT is being integrated into rationally designed combined regimens that exploit molecular responses to PDT for improved efficacy.