Normal tissue injury after cancer therapy is a local response exacerbated by an endocrine effect of TGFβ

Abstract

The sensitivity of normal tissues rather than of the tumour usually limits the effectiveness of cancer treatment. The normal tissue side effects from chemotherapy and/or radiotherapy result from both direct cellular loss and the extensive fibrosis that develops at the site of injury. Recent evidence suggests that the cytokine, transforming growth factor β (TGFβ), mediates this fibrogenic process. Herein, we provide evidence in support of the hypothesis that the fibrosis formation following therapy results not only from TGFβ produced locally in the injured normal tissue, but also from circulating TGFβ released by the tumour. Thus, therapy-induced normal tissue damage appears in part to be a local manifestation of a systemic condition.