Radiation fibrosis--current clinical and therapeutic perspectives.

Cancer survivors previously treated with curative radiotherapy are at risk of developing long-term toxicities due to radiation-induced normal tissue injury. Radiation fibrosis is an important component of the spectrum of radiation injury and at the present time treatment for this condition is limited. Data from both studies of clinical intervention and from preclinical models support the idea that fibrosis is a dynamic process and may in part be reversible. Clinical therapeutic interventions for radiation fibrosis have included empirical treatments, such as antioxidant therapies using superoxide dismutase, or vitamin E and pentoxifylline, and although evidence for therapeutic efficacy exists, further randomised studies are required. Potential therapeutic strategies that have shown promise in preclinical models include targeting pro-fibrotic cytokines such as: (1) transforming growth factor beta 1, (2) platelet-derived growth factor and its receptor tyrosine kinase and (3) connective tissue growth factor and the Rho/ROCK intracellular signalling pathway. Progress in the understanding of stem cell biology and the involvement of stem cells in radiation injury has led to the investigation of their role as a therapeutic strategy for ameliorating this disease process by promoting organ regeneration and repair. In this review we discuss the clinical and pathological features of radiation fibrosis and present the available clinical data and laboratory data relevant to these approaches to therapeutic intervention.