Photodynamic Therapy for the Treatment and Diagnosis of Cancer-A Review of the Current Clinical Status

Abstract

Photodynamic therapy (PDT) has been used as an anti-tumor treatment method for a long time and photosensitizers (PS) can be used in various types of tumors. Originally, light is an effective tool that has been used in the treatment of diseases for ages. The effects of combination of specific dyes with light illumination was demonstrated at the beginning of 20th century and novel PDT approaches have been developed ever since. Main strategies of current studies are to reduce off-target effects and improve pharmacokinetic properties. Given the high interest and vast literature about the topic, approval of PDT as the first drug/device combination by the FDA should come as no surprise. PDT consists of two stages of treatment, combining light energy with a PS in order to destruct tumor cells after activation by light. In general, PDT has fewer side effects and toxicity than chemotherapy and/or radiotherapy. In addition to the purpose of treatment, several types of PSs can be used for diagnostic purposes for tumors. Such approaches are called photodynamic diagnosis (PDD). In this Review, we provide a general overview of the clinical applications of PDT in cancer, including the diagnostic and therapeutic approaches. Assessment of PDT therapeutic efficacy in the clinic will be discussed, since identifying predictors to determine the response to treatment is crucial. In addition, examples of PDT in various types of tumors will be discussed. Furthermore, combination of PDT with other therapy modalities such as chemotherapy, radiotherapy, surgery and immunotherapy will be emphasized, since such approaches seem to be promising in terms of enhancing effectiveness against tumor. The combination of PDT with other treatments may yield better results than by single treatments. Moreover, the utilization of lower doses in a combination therapy setting may cause less side effects and better results than single therapy. A better understanding of the effectiveness of PDT in a combination setting in the clinic as well as the optimization of such complex multimodal treatments may expand the clinical applications of PDT.

Keywords: PDD–photodynamic diagnosis; PDT–photodynamic therapy; clinical application; combination (combined) therapy; photoimmunotherapy (PIT); tumor.

FIGURE 1

Phototherapy in Ancient Egypt. (A) Veneration of the sun eventually resulted in its utilization as heliotherapy (Shutterstock). (B) The Ebers Papyrus mentioned the Pharaoh’s utilization of phototherapy utilizing various plants (Ebers papyrus, University of Leipzig, Germany, https://commons.wikimedia.org, public domain) (Abdel-kader, 2016).

FIGURE 2

Timeline of PDT. The timeline shows selected applications of PDT for cancer. PDT, photodynamic therapy.

FIGURE 3

Selected Examples of First and Second Generation PSs. PS, photosensitizer.

FIGURE 4

Mechanisms of Action of PDT on Tumors. PDT can exert a plethora of actions such as inducing immune responses, direct killing of tumor cells, and damaging vascular structures.

FIGURE 5

Therapeutic Application of PDT. The patient is administered with the PS, which concentrates at the tumor. The PS is then activated by a specific light, which generates reactive oxygen species; resulting in tumor destruction. PDT, photodynamic therapy; PS, photosensitizer.

FIGURE 6

Light Sources Utilized in PDT. Laser, lamp and LED sources can be used for PDT applications. LED, light emitting diodes.

FIGURE 7

Immune Checkpoint Inhibition. Blocking of PD-1/PD-L1 or CTLA-4 with antibodies permits T cell activation. CTLA-4, cytotoxic T lymphocyte-associated protein 4; PD-1, programmed cell death protein 1; PD-L1, programmed cell death 1 ligand 1.