title: Radiation-induced fibrosis: mechanisms and implications for therapy.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Kansas Medical Center, 3901 Rainbow Boulevard, 3020A Wahl Hall East, Kansas City, KS, 66160, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Straub
authors.affiliation: Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: New
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Kansas Medical Center, 3901 Rainbow Boulevard, 3020A Wahl Hall East, Kansas City, KS, 66160, USA.
authors.forename: Chase D
authors.initials: CD
authors.lastname: Hamilton
authors.affiliation: Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, KS, 66160, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Lominska
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Kansas Medical Center, 3901 Rainbow Boulevard, 3020A Wahl Hall East, Kansas City, KS, 66160, USA.
authors.forename: Yelizaveta
authors.initials: Y
authors.lastname: Shnayder
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Kansas Medical Center, 3901 Rainbow Boulevard, 3020A Wahl Hall East, Kansas City, KS, 66160, USA. sthomas7@kumc.edu.|Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA. sthomas7@kumc.edu.|Department of Cancer Biology, University of Kansas Medical Center, Kansas City, KS, 66160, USA. sthomas7@kumc.edu.
authors.forename: Sufi M
authors.initials: SM
authors.lastname: Thomas
mesh_terms: D004249:DNA Damage / Q000528:radiation effects; D005355:Fibrosis; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D009369:Neoplasms / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D011878:Radiotherapy / Q000009:adverse effects; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016212:Transforming Growth Factor beta
keywords: Cancer; Fibroblast; Fibrosis; Inflammation; Radiation; TGF-β; Therapy