Impact of radiation therapy on healthy tissues.

Radiation therapy has a fundamental role in the management of cancers. However, despite a constant improvement in radiotherapy techniques, the issue of radiation-induced side effects remains clinically relevant. Mechanisms of acute toxicity and late fibrosis are therefore important topics for translational research to improve the quality of life of patients treated with ionizing radiations. Tissue changes observed after radiotherapy are consequences of complex pathophysiology, involving macrophage activation, cytokine cascade, fibrotic changes, vascularization disorders, hypoxia, tissue destruction and subsequent chronic wound healing. Moreover, numerous data show the impact of these changes in the irradiated stroma on the oncogenic process, with interplays between tumor radiation response and pathways involved in the fibrotic process. The mechanisms of radiation-induced normal tissue inflammation are reviewed, with a focus on the impact of the inflammatory process on the onset of treatment-related toxicities and the oncogenic process. Possible targets for pharmacomodulation are also discussed.