Photodynamic Therapy (PDT) has proved to be one of the most effective treatments for skin cancer. PDT is based on lights and comprises a non-invasive treatment. It results in greater precision along with favored outcomes. This review discusses the development of PDT, underlying mechanisms, recent advances, and the role of PDT in the present dermatologic oncology. 

Understanding Photodynamic Therapy (PDT)

PDT describes a treatment regime that includes a photo-sensitizing agent and a specific wavelength of light so as to induce selective cytotoxicity in tissues. This comprises three principal components:  

  • Photosensitizer: The photosensitizer is defined as a chemical compound having an affinity for malignant or dysplastic cells.  
  • Light Source:Typical light source for Photodynamic Therapy (PDT) comprises either lasers or light-emitting diodes (LEDs), both emitting light at suitable wavelengths where the photosensitizer exhibits its peak absorption.
  • Oxygen: The presence of tissues oxygenized by the excited photo-sensitizer induces the production of radical oxygen species (ROS), leading to cell death (Baskaran et al., 2018). 

Activation of the photosensitizer occurs by the relevant light source, after which the photosensitizer will then be in an excited state, in which it ultimately transfers energy to molecular oxygen to produce ROS that may cause localized damage to cellular components or induce cell death. In such cases, the surrounding healthy tissue is spared the mechanism used to target destruction to cancerous cells (Baskaran et al., 2018). 

Advancements in Photosensitizers

The effectiveness of PDT is highly dependent on the characteristics of the photosensitizer in use. Recent developments have seen second- and third-generation photosensitizers developed with improved propertiesfor PDT that include: 

  • Greater Selectivity: Therefore, newer photosensitizers showed greater selectivity for tumour cells and less damage to healthy tissues (de Berker et al., 2007).  
  • Better Pharmacokinetics: Changes in the chemical structure have thus created a new generation of photosensitizers which have fairly rapid clearance, thus limiting prolonged photosensitivity of the patient (Baskaran et al., 2018).  
  • Longer-Wavelength Activation: Technological advances have given rise to photosensitizers with the capacity of being activated by longer wavelengths, penetrating deeper into the tissue, and treating thicker lesions (Szeimies et al., 2010). 

Innovations in Light Delivery Systems

The efficiency of PDT varies per each delivery mechanism of light. Conventional sources of light-in particular, lasers-have their advantages in tight wavelength specificity, but tend to be expensive and not readily available. The new therapy with light-emitting diodes (LEDT) seems to be quite versatile and offers a cheaper alternative. LEDT devices could emit specific wavelengths that could activate photosensitizers and have found utility in managing conditions such as actinic keratosis and superficial basal cell carcinomas (Dodds et al., 2014). 

Clinical Applications and Efficacy

PDT is being tremendously useful on all forms and types of skin carcinomas: 

  • Actinic Keratosis (AK): A sort of skin precancerous lesion that progresses to squamous cell carcinoma. PDT has proven to very effective for the clearance of AK lesions and studies show it provides improved cosmetic result compared to other interventions such as cryotherapy (Dodds et al., 2014).   
  • Basal Cell Carcinomas (BCC): It is the most common type of skin cancer. Such lesions can be treated using PDT as a non-surgical option offering a radical cure for superficial BCC that competes with surgery in terms of cure rate and offers superb cosmetic results (Baskaran et al., 2018).  
  • Squamous Cell Carcinoma (SCC) in situ: Bowen’s disease is the same. PDT is an effective way to treat SCC in situ as an alternative to more invasive surgical procedures (Szeimies et al., 2010). 

Advantages of PDT

The advantages of PDT over traditional therapies account for the significantly increased interest in the new avenue of PDT:  

  • Non-Invasive: As PDT does not involve incisions, this decreases the possibility of infection or scarring (de Berker et al., 2007).  
  • Selective Cytotoxicity: PDT is representing a selective treatment that will cause the least damage to the adjacent healthy tissues (Baskaran et al., 2018).  
  • Repeatable: PDT can be used safely again at that site if needed, which is good in the case of lesions that recur (Szeimies et al., 2010).  
  • Better Cosmetic Result: Patients usually are favored regarding these methods, presenting worse cosmetic outcomes than surgery (Dodds et al., 2014). 

Challenges and Future Directions

Even though PDT has its advantages, the aspect of more limitations includes the following: 

Limited Penetration Depth: PDT is effective for superficial lesions only; this is due to the limited penetration of light, which does not make it ideal for thicker tumors (Baskaran et al., 2018).

Photosensitivity: Photosensitization can lead to some forms of temporary photosensitivity that suggests patients stay away from direct sunlight immediately after the treatment (Szeimies et al., 2010).  

All promising methodologies should also try to focus on overcoming the aforementioned limitations by coming up with photosensitizers that can be activated using near-infrared light, which is able to reach deeper tissues, and also studies being undertaken into combining PDT with other therapeutic modalities such as immunotherapy to enhance the overall efficacy (Baskaran et al., 2018). 

Conclusion 

Photodynamic Therapy is a breakthrough in non-invasive treatment for skin cancers. It continues to develop with the advent of new photosensitizers and techniques for delivering comparable increasing clinical applications. Further studies will very likely put PDT into a major place in dermatological oncology and provide effective treatments with few side effects and with excellent cosmetic outcomes. 

References

  1. Baskaran, R., Lee, J., & Yang, S.-G. (2018). Clinical development of photodynamic agents and therapeutic applications. Biomaterials Research, 22, Article 25. https://doi.org/10.1186/s40824-018-0140-z 
  2. Dodds, A., Chia, A., & Shumack, S. (2014). Actinic keratosis: Rationale and management. Dermatology and Therapy, 4(1), 11–31. https://doi.org/10.1007/s13555-014-0049-2 
  3. de Berker, D., McGregor, J. M., & Hughes, B. R. (2007). Guidelines for the management of actinic keratoses. British Journal of Dermatology, 156(2), 222–230. https://doi.org/10.1111/j.1365-2133.2006.07663.x 
  4. Szeimies, R.-M., Radny, P., Sebastian, M., Borrosch, F., Dirschka, T., & Mensing, H. (2010). Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: Results of a prospective, randomized, multicenter clinical phase III study comparing BF-200 ALA and methyl-aminolevulinate. British Journal of Dermatology, 163(1), 44–49. https://doi.org/10.1111/j.1365-2133.2010.09708.x 

 

 

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