Oxygen, a toxic agent

In concrete terms the PS present in the malignant cancerous cells absorbs this red light, becomes excited and transmits the energy to molecular oxygen O₂. There follows a series of reactions within the cells leading to the formation of reactive oxygen species. The reactive species derived from oxygen which is formed by energy transfer is singlet oxygen, ¹O₂. The latter has a short life span but is very destructive to cells. It reacts with amino acids, oxidizes lipids, alters proteins, the mitochondrions or the cell nuclei and causes irreversible damage to DNA. It is the real cytotoxic agent of PDT.  These photodynamic reactions cause tissue necrosis,  apoptosis and autophagy of the malignant cancer cells. They also have indirect effects which increase the effectiveness of treatment such as the destruction of tumour vascularisation and the induction of inflammatory and immune reactions.

For their part the malignant cells have cell protection mechanisms to limit the cytotoxic effects of PDT. In trying to understand these mechanisms, the GIGA Research Unit’s Laboratory of Virology and Immunology has brought to light the role played by several enzymes which control cell defence mechanisms. In inhibiting these enzymes it is thus possible to deprive malignant cells of their defences. ‘The results obtained concerning glioblastoma, which are amongst the most aggressive brain tumours, shows that the inhibition of certain key enzymes increases very significantly the tumour’s sensitivity to PDT,’ says Jacques Piette enthusiastically.