Novel strategies to prevent, mitigate or reverse radiation injury and fibrosis

Abstract

Despite recent advances in Radiation Oncology with treatment planning and delivery of image-guided radiation therapy, acute tissue toxicity is still a doselimiting factor for optimal local tumor control. Additionally, as the number of long- term cancer survivors is increasing, unacceptable complications emerge and dramatically impair the patients’ quality of life. This means patients and clinicians expect therapeutic management of radiation-induced complications. Over the past four decades, research has enhanced our understanding of the pathophysiological, cellular and molecular processes governing normal tissue toxicity. This knowledge has provided us with tools to improve the therapeutic ratio of radiation therapy by enhancing its tumoricidal effect and protecting normal tissue. In this chapter, we review biology-driven efforts to develop translatable therapeutic approaches to prevent, mitigate or reverse radiation injury based upon cellular and signalling pathways targeting. We also highlight innovative approaches based upon manipulating external contributors such as the microbiota and applying novel radiotherapy delivery procedures.