Photodynamic Therapy for the Treatment of Glioblastoma

Photodynamic therapy (PDT) uses non-toxic photosensitizers and harmless visible light in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumour microvasculature and stimulate the host immune system. In contrast to surgery, radiotherapy and chemotherapy that are mostly immunosuppressive, PDT causes acute inflammation, expression of heat-shock proteins, invasion and infiltration of the tumour by leukocytes, and might increase the presentation of tumour-derived antigens to T cells.

Photodynamic therapy (PDT) has been used for many years, but it is only now becoming widely accepted and utilized. Originally it was developed as a tumor therapy and some of its most successful applications are for non-malignant diseases. This article provides a broad review of different parameters used and mechanisms instituted in PDT such as photosensitizers (PS), photochemistry and photophysics, cellular localization, cellular signaling, cell metabolism and modes of cell death that operate on a cellular level, as well as photosensitizer pharmacokinetics, biodistribution, tumor localization and modes of tumor destruction. These specific cellular mechanisms are most commonly applied in PDT and for the most part are often researched and exploited. If the combination of these specific parameters and mechanisms can be optimized within PDT it could possibly be used as a suitable alternative for the treatment and management of specific cancers.

In contrast to almost all other brain tumors, diffuse gliomas infiltrate extensively in the neuropil. This growth pattern is a major factor in therapeutic failure. Diffuse infiltrative glioma cells show some similarities with guerilla warriors. Histopathologically, the tumor cells tend to invade individually or in small groups in between the dense network of neuronal and glial cell processes. Meanwhile, in large areas of diffuse gliomas the tumor cells abuse pre-existent “supply lines” for oxygen and nutrients rather than constructing their own. Radiological visualization of the invasive front of diffuse gliomas is difficult. Although the knowledge about migration of (tumor)cells is rapidly increasing, the exact molecular mechanisms underlying infiltration of glioma cells in the neuropil have not yet been elucidated. As the efficacy of conventional methods to fight diffuse infiltrative glioma cells is limited, a more targeted (“search & destroy”) tactic may be needed for these tumors. Hopefully, the study of original human glioma tissue and of genotypically and phenotypically relevant glioma models will soon provide information about the Achilles heel of diffuse infiltrative glioma cells that can be used for more effective therapeutic strategies.