Photodynamic therapy mediates antitumor effects through multiple non‑apoptotic cell death pathways.

Area of Science:

• Oncology
• Biochemistry
• Immunology

Background:

• Photodynamic therapy (PDT) utilizes light-activated compounds to induce cell death.
• Tumor cells often develop resistance to apoptosis, limiting conventional therapies.
• PDT's ability to trigger diverse cell death mechanisms offers a promising strategy against resistant tumors.

Purpose of the Study:

• To review non-apoptotic cell death pathways activated by PDT.
• To discuss the mechanisms underlying these cell death processes.
• To explore clinical applications and challenges of PDT in cancer treatment.

Main Methods:

• Literature review of studies on PDT and cell death.
• Analysis of mechanisms including autophagic cell death, regulated necrosis, ferroptosis, pyroptosis, and paraptosis.
• Examination of current challenges and future directions in PDT research.

Main Results:

• PDT activates multiple non-apoptotic pathways: autophagic cell death, regulated necrosis, ferroptosis, pyroptosis, and paraptosis.
• These pathways contribute to tumor eradication and stimulate anti-tumor immunity.
• Key challenges include controlling reactive oxygen species (ROS), mitigating hypoxia, and ensuring targeted photosensitizer delivery.

Conclusions:

• PDT offers a versatile approach to circumventing apoptosis resistance by engaging diverse cell death modalities.
• Nanotechnology, hypoxia-responsive agents, and combination therapies show potential to overcome PDT limitations.
• Future research should focus on targeted photosensitizers, advanced light delivery, and personalized treatment regimens for enhanced efficacy.