Molecular Effectors of Photodynamic Therapy-Mediated Resistance to Cancer Cells
Eric Chekwube Aniogo1, Blassan P George1, Heidi Abrahamse1
1Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein 2028, South Africa.
Abstract:
Photodynamic therapy (PDT) is currently enjoying considerable attention as the subject of experimental research to treat resistant cancers. The preferential accumulation of a non-toxic photosensitizer (PS) in different cellular organelles that causes oxidative damage by combining light and molecular oxygen leads to selective cell killing. However, one major setback, common among other treatment approaches, is tumor relapse and the development of resistance causing treatment failure. PDT-mediated resistance could result from increased drug efflux and decreased localization of PS, reduced light exposure, increased DNA damage repair, and altered expression of survival genes. This review highlights the essential insights of PDT reports in which PDT resistance was observed and which identified some of the molecular effectors that facilitate the development of PDT resistance. We also discuss different perceptions of PDT and how its current limitations can be overturned to design improved cancer resistant treatments.
Insights
Photodynamic therapy (PDT) shows promise for resistant cancers by selectively killing cells. However, tumor relapse and resistance can occur due to various molecular mechanisms, necessitating improved treatment strategies.
Area of Science:
- Oncology
- Biochemistry
- Photomedicine
Background:
- Photodynamic therapy (PDT) utilizes photosensitizers, light, and oxygen for selective cancer cell killing.
- PDT is under investigation for treating drug-resistant cancers.
- Tumor relapse and resistance are significant challenges limiting PDT efficacy.
Purpose of the Study:
- To review molecular mechanisms underlying resistance to photodynamic therapy (PDT).
- To identify molecular effectors involved in PDT resistance.
- To discuss strategies for overcoming PDT limitations in cancer treatment.
Main Methods:
- Literature review of experimental PDT reports.
- Analysis of studies identifying mechanisms of PDT resistance.
- Synthesis of findings on molecular effectors and resistance pathways.
Main Results:
- PDT resistance can arise from increased drug efflux, reduced photosensitizer localization, and enhanced DNA repair.
- Altered expression of survival genes contributes to treatment failure.
- Specific molecular effectors facilitating PDT resistance have been identified.
Conclusions:
- Understanding PDT resistance mechanisms is crucial for developing effective cancer therapies.
- Strategies to overcome PDT resistance are needed to improve treatment outcomes.
- Further research can guide the design of improved PDT-based cancer treatments.
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