Targeting TGF-β as a Strategy to Ameliorate Intestinal Side Effects of Radiation Therapy

The number of cancer survivors in the US is increasing exponentially and currently approaches 10 million. While long-term cancer survivors may be cured of their original malignancies, some suffer from treatment-related side effects. Radiation injury of normal tissues, particularly radiation-induced fibrosis, is a major contributor to long-term morbidity after cancer therapy. Among the fibrogenic factors that have been investigated in the context of radiation fibrosis, transforming growth factor-β (TGF-β) appears to play a particularly central role. Consequently, considerable efforts have been directed toward targeting TGF-β or TGF-∇ signaling as a strategy to prevent or treat radiation fibrosis. This chapter discusses the clinical significance of long-term side effects after cancer therapy with special emphasis on intestinal radiation fibrosis. Existing evidence in support of a mechanistic role for TGF-β is introduced and discussed, and various approaches by which chronic radiation fibrosis may be ameliorated by inhibition of the TGF-β signaling pathway are presented.