Review 10.1586/14737140.5.5.791 © 2005 Future Drugs Ltd ISSN 1473-7140 791 www.future-drugs.com Photodynamic therapy in dermatology: current concepts in the treatment of skin cancer Jorge Garcia-Zuazaga, Kevin D Cooper and Elma D Baron † † Author for correspondence Louis Stokes Veterans Affairs Medical Center, Cleveland, OH, USA Tel.: +1 216 368 4971 Fax: +1 216 368 0212 Elma.Baron@case.edu KEYWORDS: aminolevulinic acid, photodynamic therapy, photosensitizer, skin cancer Photodynamic therapy is a treatment modality that is developing rapidly and increasing in utilization within various medical specialties, including dermatology. This technique requires the presence of a photosensitizer, light energy and molecular oxygen to selectively destroy pathologic cells. A thorough understanding of photobiology and tissue optics is necessary to correctly and effectively utilize photodynamic therapy in dermatology. Photodynamic therapy has been approved by the US Food and Drug Administration to treat actinic keratoses. In Europe, photodynamic therapy is currently being used in the treatment of actinic keratoses and basal cell carcinoma. Other off-label uses of photodynamic therapy have included cutaneous lesions of Bowen’s disease, psoriasis, cutaneous T-cell lymphoma and acne. Most recently, photodynamic therapy has been employed in photorejuvenation. The advantages of photodynamic therapy include the capacity for noninvasive targeted therapy via topical application of the drug and local irradiation of involved areas, as well as the ability to generate excellent cosmetic results with minimal discomfort. This review summarizes the fundamentals of photodynamic therapy and its role in the treatment of cutaneous disorders, particularly skin malignancies. Expert Rev. Anticancer Ther. 5(5), 791–800 (2005) History of photodynamic therapy Photodynamic therapy (PDT ) has been used successfully in various fields of medicine, including oncology, ophthalmology and der- matology. PDT use in dermatology, in particu- lar, has increased in popularity during the last 10 years, mainly due to increased understand- ing of photobiology and skin tissue optics. TABLE 1 summarizes the evolution of PDT over the last 100 years. Basic principles of photodynamic therapy Photobiology T he therapeutic challenges for light-based therapy and PDT rely on a thorough under- standing of tissue optics and photobiologic reactions. Determining how to selectively deliver photons and induce photodamage to specific targets within pathologic cells, as well as the generation of appropriate response from the tissue are critical for successful PDT. When a photon of light reaches the skin, it must follow one of three basic principles: reflection, scattering or absorption [4]. Reflected light aids in the diagnosis of skin dis- eases, but may not have a biologic effect. Tis- sue scattering of light is wavelength and target dependent. In general, target cells that are deeper in the skin require delivery of light at a longer wavelength. Absorption is defined as the transfer of energy from light to tissue. In PDT, this is the rate-limiting step, since in the absence of photon absorption into target cells, there can be no biologic or therapeutic effects. Absorption of light is dependent on both the wavelength and properties of the chromophore (i.e., light-absorbing molecule) [4,5]. In PDT, the photosensitizing agent acts as the chromophore. In order for a given photon of light to have a therapeutic effect it must first reach the target molecule within the skin, and then be absorbed by a specific chromophore within CONTENTS History of photodynamic therapy Basic principles of photodynamic therapy Aminolevulinic acid-based photodynamic therapy Safety & side-effect profile Aminolevulinic acid esters: methylaminoevulinic acid Photodynamic therapy uses in dermatology New applications of photodynamic therapy Expert commentary Five-year view Key issues References Affiliations For reprint orders, please contact reprints@future-drugs.com