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Radiation-induced fibrosis: mechanisms and implications for therapy

  • Review – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Radiation-induced fibrosis (RIF) is a long-term side effect of external beam radiation therapy for the treatment of cancer. It results in a multitude of symptoms that significantly impact quality of life. Understanding the mechanisms of RIF-induced changes is essential to developing effective strategies to prevent long-term disability and discomfort following radiation therapy. In this review, we describe the current understanding of the etiology, clinical presentation, pathogenesis, treatment, and directions of future therapy for this condition.

Methods

A literature review of publications describing mechanisms or treatments of RIF was performed. Specific databases utilized included PubMed and clinicaltrials.gov, using keywords “Radiation-Induced Fibrosis,” “Radiotherapy Complications,” “Fibrosis Therapy,” and other closely related terms.

Results

RIF is the result of a misguided wound healing response. In addition to causing direct DNA damage, ionizing radiation generates reactive oxygen and nitrogen species that lead to localized inflammation. This inflammatory process ultimately evolves into a fibrotic one characterized by increased collagen deposition, poor vascularity, and scarring. Tumor growth factor beta serves as the primary mediator in this response along with a host of other cytokines and growth factors. Current therapies have largely been directed toward these molecular targets and their associated signaling pathways.

Conclusion

Although RIF is widely prevalent among patients undergoing radiation therapy and significantly impacts quality of life, there is still much to learn about its pathogenesis and mechanisms. Current treatments have stemmed from this understanding, and it is anticipated that further elucidation will be essential for the development of more effective therapies.

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Acknowledgments

The Department of Otolaryngology-Head and Neck Surgery at the University of Kansas Medical Center, the University of Kansas Cancer Center’s CCSG (1-P30-CA168524-02), and the Kansas Intellectual and Developmental Disabilities Center (NICHD HD00258) were the funding sources. The authors acknowledge Mr. Phil Shafer for generating the schematic diagram. We apologize to authors whose work was not cited due to space constraints.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, University of Kansas Medical Center, 3901 Rainbow Boulevard, 3020A Wahl Hall East, Kansas City, KS, 66160, USA

    Jeffrey M. Straub, Chase D. Hamilton, Yelizaveta Shnayder & Sufi M. Thomas

  2. Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA

    Jacob New & Sufi M. Thomas

  3. Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, KS, 66160, USA

    Chris Lominska

  4. Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA

    Sufi M. Thomas

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  1. Jeffrey M. Straub
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Correspondence to Sufi M. Thomas.

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Straub, J.M., New, J., Hamilton, C.D. et al. Radiation-induced fibrosis: mechanisms and implications for therapy. J Cancer Res Clin Oncol 141, 1985–1994 (2015). https://doi.org/10.1007/s00432-015-1974-6

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