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Epigenetics in radiation-induced fibrosis

Oncogene volume 34, pages 2145–2155 (2015)Cite this article

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Abstract

Radiotherapy is a major cancer treatment option but dose-limiting side effects such as late-onset fibrosis in the irradiated tissue severely impair quality of life in cancer survivors. Efforts to explain radiation-induced fibrosis, for example, by genetic variation remained largely inconclusive. Recently published molecular analyses on radiation response and fibrogenesis showed a prominent role of epigenetic gene regulation. This review summarizes the current knowledge on epigenetic modifications in fibrotic disease and radiation response, and it points out the important role for epigenetic mechanisms such as DNA methylation, microRNAs and histone modifications in the development of this disease. The synopsis illustrates the complexity of radiation-induced fibrosis and reveals the need for investigations to further unravel its molecular mechanisms. Importantly, epigenetic changes are long-term determinants of gene expression and can therefore support those mechanisms that induce and perpetuate fibrogenesis even in the absence of the initial damaging stimulus. Future work must comprise the interconnection of acute radiation response and long-lasting epigenetic effects in order to assess their role in late-onset radiation fibrosis. An improved understanding of the underlying biology is fundamental to better comprehend the origin of this disease and to improve both preventive and therapeutic strategies.

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Acknowledgements

We apologize to all researchers whose relevant contributions were not cited due to space limitations. This work was supported by a grant from the Deutsche Krebshilfe, project number 109394. CW holds a stipend from the Helmholtz International Graduation School for Cancer Research.

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  1. Department of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany

    C Weigel, P Schmezer, C Plass & O Popanda

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Weigel, C., Schmezer, P., Plass, C. et al. Epigenetics in radiation-induced fibrosis. Oncogene 34, 2145–2155 (2015). https://doi.org/10.1038/onc.2014.145

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