Targeting the TGF-beta 1 Pathway to Prevent Normal Tissue Injury After Cancer Therapy

With > 10,000,000 cancer survivors in the U. S. alone, the late effects of cancer treatment are a significant public health issue. Over the past 15 years, much work has been done that has led to an improvement in our understanding of the molecular mechanisms underlying the development of normal tissue injury after cancer therapy. In many cases, these injuries are characterized at the histologic level by loss of parenchymal cells, excessive fibrosis, and tissue atrophy. Among the many cytokines involved in this process, transforming growth factor (TGF)-beta 1 is thought to play a pivotal role. TGF-beta 1 has a multitude of functions, including both promoting the formation and inhibiting the breakdown of connective tissue. It also inhibits epithelial cell proliferation. TGF-beta 1 is overexpressed at sites of injury after radiation and chemotherapy. Thus, TGF-beta 1 represents a logical target for molecular therapies designed to prevent or reduce normal tissue injury after cancer therapy. Herein, the evidence supporting the critical role of TGF-beta 1 in the development of normal tissue injury after cancer therapy is reviewed and the results of recent research aimed at preventing normal tissue injury by targeting the TGF-beta 1 pathway are presented. The Oncologist 2010; 15: 350-359