Systematic Review of Photodynamic Therapy in Gliomas

SIMPLE SUMMARY: Malignant gliomas are of the deadliest, most hard-to-treat cancers, given their various characteristics of aggression and infiltration as well as the location of growth. Photodynamic therapy (PDT) is a promising avenue for localized cancer therapy. A therapeutic effect is achieved by systemic drug delivery followed by localized wavelength-specific illumination. This review extensively explores the use of photosensitizers in gliomas, from their first use to the present, and details their mechanisms, and pre-clinical and clinical findings. Further discussion is provided on its limitations and future directions. ABSTRACT: Over the last 20 years, gliomas have made up over 89% of malignant CNS tumor cases in the American population (NIH SEER). Within this, glioblastoma is the most common subtype, comprising 57% of all glioma cases. Being highly aggressive, this deadly disease is known for its high genetic and phenotypic heterogeneity, rendering a complicated disease course. The current standard of care consists of maximally safe tumor resection concurrent with chemoradiotherapy. However, despite advances in technology and therapeutic modalities, rates of disease recurrence are still high and survivability remains low. Given the delicate nature of the tumor location, remaining margins following resection often initiate disease recurrence. Photodynamic therapy (PDT) is a therapeutic modality that, following the administration of a non-toxic photosensitizer, induces tumor-specific anti-cancer effects after localized, wavelength-specific illumination. Its effect against malignant glioma has been studied extensively over the last 30 years, in pre-clinical and clinical trials. Here, we provide a comprehensive review of the three generations of photosensitizers alongside their mechanisms of action, limitations, and future directions.