Photodynamic therapy for glioblastoma: a narrative review

Glioblastoma (GBM) remains one of the most aggressive primary brain tumors with poor survival outcomes and a lack of approved therapies. A promising novel approach for GBM is the application of photodynamic therapy (PDT), a localized, light-activated treatment using tumor-selective photosensitizers. This narrative review describes the mechanisms, delivery systems, photosensitizers, and available evidence regarding the potential of PDT as a novel therapeutic approach for GBM.

A comprehensive review of the preclinical and clinical literature was conducted on the role of PDT for GBM. Special emphasis was placed on PDT's mechanisms of action, immunomodulatory effects, delivery systems, and combinatorial potential with other treatment regimens. All clinical trials on this topic were reviewed and described.

PDT exerts tumor-specific cytotoxic effects via reactive oxygen species generation, vascular disruption, and immune activation. Photosensitizers such as 5-aminolevulinic acid (5-ALA), chlorins, and phthalocyanines demonstrate selective accumulation in glioma cells and enhance treatment precision. Preclinical studies demonstrate that PDT can induce apoptosis, improve blood-brain barrier permeability, and synergize with existing chemotherapeutics. Early-phase clinical trials, including the INDYGO and talaporfin sodium-based studies, report promising safety profiles and extended survival in newly diagnosed and recurrent GBM patients.

PDT offers a novel targeted approach for improving local control of GBM. With continued innovation in photosensitizer design, delivery technologies, and combinatorial strategies, PDT holds promise as a viable therapeutic adjunct in GBM treatment. Further clinical validation through randomized controlled trials is warranted to establish its efficacy and gain regulatory approval with the eventual goal of integration into standard neuro-oncology practice.