Photodynamic therapy (PDT)
Photodynamic therapy (PDT) is an innovative treatment modality primarily for local precancerous and cancerous lesions, particularly those of epithelial origin. The technique utilizes photosensitizers, which are light-sensitive drugs that accumulate in cancer cells. Upon activation by specific wavelengths of light, usually delivered via laser, these drugs generate reactive oxygen species (ROS) that damage cancer cells, ultimately leading to their destruction through apoptosis. PDT is minimally invasive and can also be applied to nonmalignant conditions, such as wet age-related macular degeneration.
Common cancers treated with PDT include esophageal, lung, bladder, nonmelanoma skin, head and neck, pancreatic, bile duct, prostate, and vaginal cancers. While the light activating the photosensitizers only penetrates superficially, limiting PDT's application to smaller tumors, ongoing research and advancements in nanotechnology are enhancing its effectiveness and targeting capabilities. Some photosensitizers are undergoing clinical trials to further expand treatment options. However, patients may experience side effects, including increased sensitivity to light and other mild adverse reactions. Overall, PDT represents a promising approach in cancer treatment, particularly when combined with other therapeutic modalities.
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Photodynamic therapy (PDT)
ATC CODE: L01XD
DEFINITION: Photodynamic therapy (PDT) is a modality for treating local precancerous and cancerous lesions of epithelial origin. The technology relies on a class of anticancer drugs called photosensitizers that become active when exposed to specific light wavelengths, usually from a laser beam. Minimally invasive, PDT is also used to treat nonmalignant diseases, particularly the ocular condition known as wet age-related macular degeneration.
Cancers treated:Esophageal cancer, lung cancer, bladder carcinoma, nonmelanoma skin cancer, head and neck cancers, pancreatic cancer, bile duct cancer, prostate cancer, vaginal cancer
Subclasses of this group: The most-used photosensitizers include phthalocyanines, chlorin, and bacteriochlorin, along with both natural and synthetic nontoxic dyes such as riboflavin, hypocrellin, and curcumin. According to the American Cancer Society, the photosensitizing agents photofrin, porfimer sodium, temoporfin, aminolevulinic acid (ALA), and methyl ester of ALA were approved by the US Food and Drug Administration. Motexafin lutetium, palladium bacteriopheophorbide, purlytin, verteporfin, and talaporfin were undergoing clinical trials in the mid-2020s.
Delivery routes: Intravenous or topical, depending on the drug’s chemical structure, the type of cancer, and its location
How these drugs work: The first clinical application of PDT was reported in 1903 by two German researchers, who used a topical coal tar dye called eosin in combination with visible light to treat skin cancer. The isolation of safer and more effective photosensitive dyes, called porphyrins, has propelled the field forward. Photosensitizers preferentially accumulate in abnormal tissues and cause little damage to surrounding healthy cells.
PDT is a two-part process. First, a nontoxic photosensitizer is administered to the patient. The lesion site is then exposed to light of a suitable wavelength to excite the photosensitive drug. Activated drug molecules initiate cytotoxic reactions that destroy tumor cells. They transfer energy to molecular oxygen, generating reactive oxygen species (ROS), such as singlet oxygen. These active molecular species damage deoxyribonucleic acid (DNA) and cause the oxidation of proteins and lipids. As a result, cancer cells undergo or apoptosis, the natural process of cell death. Because the light needed to activate most photosensitizers cannot penetrate deeply into tissue, the therapeutic potential of PDT is limited to the treatment of local superficial tumors rather than large tumors or metastases.
Research into PDT continued as the twenty-first century progressed. Nanotechnology, such as the use of quantum dots, has improved PDT by improving the delivery and activation methods of the photosensitizers. This has made PDT more effective in targeting specific cancer cells. Tumors that have been resistant to PDT therapy in the past are now more effectively treated by the procedure due to the development of oxygen-independent photosynthesizers, which can operate without oxygen in hypoxic tumor conditions. Combing PDT with other therapies, including immunotherapy, chemotherapy, and radiation, has also increased its effectiveness.
Side effects: One side effect of PDT is increased sensitivity to light (sunburn-like reactions), which may last several weeks after administration. Other side effects include constipation, irritation at the injection site, back pain, chest pain, fever, flu-like syndrome, and general weakness.
Bibliography
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Tang, Yufu, et al. "Oxygen-independent Organic Photosensitizer with Ultralow-power NIR Photoexcitation for Tumor-specific Photodynamic Therapy." Nature Communications, vol. 15, no. 1, 2024, pp. 1-13, doi.org/10.1038/s41467-024-46768-w. Accessed 28 June 2024.