Photodynamic Therapy in Glioblastoma: Current Insights and Emerging Molecular Targets

Abstract Glioblastoma (GBM), a highly aggressive and treatment-refractory tumour of the central nervous system, remains one of the most difficult cancers to treat. Despite significant advancements in surgery, radiation therapy, and chemotherapy, GBM's inherent resistance mechanisms result in poor prognosis and high recurrence rates. Photodynamic therapy (PDT), a promising treatment strategy based on the activation of photosensitizers with light to generate reactive oxygen species (ROS), offers a potential alternative to conventional therapies. However, its clinical application is constrained by limited light penetration, tumour heterogeneity, and resistance mechanisms. Recent insights into the molecular biology of GBM, particularly the role of ubiquitination and deubiquitination in regulating cellular responses to PDT, have opened new avenues for optimizing treatment efficacy. This review examines the mechanisms underlying PDT-induced cell death, the role of ubiquitination in modulating PDT responses, and the potential for enhancing PDT through novel molecular targets and combination approaches.