Mechanisms of radiation-induced skin injury and implications for future clinical trials

Abstract

Purpose: To summarize current knowledge regarding mechanisms of radiation-induced skin injury and medical countermeasures available to reduce its severity. Advances in radiation delivery using megavoltage and intensity modulated radiation therapy have permitted delivery of higher doses of radiation to well-defined tumor target tissues. Although skin is not a radiation dose-limiting tissue, injury to skin poses substantial morbidity risks in the curative treatment of cancers, especially when radiation is administered in combination with chemotherapy. In the continuum of radiation-induced skin injury, late effects are most severe being characterized by sub-cutaneous fibrosis and morbidity. The principal pathogenesis is initiated by depletion of acutely responding epithelial tissues and damage to vascular endothelial microvessels. Emerging concepts of radiation- induced skin injury suggest that the recovery of stromal stem cells and tissue repair remain chronically impaired by long-lived free radicals, reactive oxygen species, and pro-inflammatory cytokines/chemokines resulting in progressive damage after radiation exposure.

Conclusions: As pathways underlying the cellular and molecular mechanisms of radiation-induced skin injury are becoming better understood, novel approaches are being developed for mitigating or treating the associated pathogenesis.

Keywords::

• Radiation
• cutaneous
• injury
• mechanism

Acknowledgements

The authors appreciate the helpful discussion provided by Dr Samuel Ryu. The authors also wish to thank the reviewers for their insight and direction to improve the manuscript.

Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

The authors acknowledge National Institutes of Health grant support NIH R21-ES019251 (JHK) that partially funded the work presented. Patents for the use of HDAC inhibitors and stem cell mobilizers are held by some of the authors (JHK, AK, SLB) and the exclusive licenses for their use as mitigators of radiation cutaneous injury are held by their commercial partners, Humanetics Corp. Inc., Minnesota, USA, in exchange for royalties.