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Journal of Cancer Research and Clinical Oncology

, Volume 141, Issue 11, pp 1985–1994 | Cite as

Radiation-induced fibrosis: mechanisms and implications for therapy

  • Jeffrey M. Straub
  • Jacob New
  • Chase D. Hamilton
  • Chris Lominska
  • Yelizaveta Shnayder
  • Sufi M. ThomasEmail author
Review – Clinical Oncology

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.

Keywords

Cancer Radiation Fibrosis Fibroblast Inflammation TGF-β Therapy 

Notes

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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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Jeffrey M. Straub
    • 1
  • Jacob New
    • 2
  • Chase D. Hamilton
    • 1
  • Chris Lominska
    • 3
  • Yelizaveta Shnayder
    • 1
  • Sufi M. Thomas
    • 1
    • 2
    • 4
    Email author
  1. 1.Department of Otolaryngology-Head and Neck SurgeryUniversity of Kansas Medical CenterKansas CityUSA
  2. 2.Department of Anatomy and Cell BiologyUniversity of Kansas Medical CenterKansas CityUSA
  3. 3.Department of Radiation OncologyUniversity of Kansas Medical CenterKansas CityUSA
  4. 4.Department of Cancer BiologyUniversity of Kansas Medical CenterKansas CityUSA

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