The clinical manifestations and molecular pathogenesis of radiation fibrosis

Mackenzie Fijardo; Jennifer Yin Yee Kwan; Pierre-Antoine Bissey; Deborah E Citrin; Kenneth W Yip; Fei-Fei Liu

doi:10.1016/j.ebiom.2024.105089

The clinical manifestations and molecular pathogenesis of radiation fibrosis

EBioMedicine. 2024 Apr 4:103:105089. doi: 10.1016/j.ebiom.2024.105089. Online ahead of print.

Authors

Mackenzie Fijardo¹, Jennifer Yin Yee Kwan², Pierre-Antoine Bissey³, Deborah E Citrin⁴, Kenneth W Yip¹, Fei-Fei Liu⁵

Affiliations

¹ Research Institute, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.
² Research Institute, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
³ Research Institute, Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
⁴ Radiation Oncology Branch, National Cancer Institute, Bethesda, MD, United States of America.
⁵ Research Institute, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. Electronic address: fei-fei.liu@rmp.uhn.ca.

Abstract

Advances in radiation techniques have enabled the precise delivery of higher doses of radiotherapy to tumours, while sparing surrounding healthy tissues. Consequently, the incidence of radiation toxicities has declined, and will likely continue to improve as radiotherapy further evolves. Nonetheless, ionizing radiation elicits tissue-specific toxicities that gradually develop into radiation-induced fibrosis, a common long-term side-effect of radiotherapy. Radiation fibrosis is characterized by an aberrant wound repair process, which promotes the deposition of extensive scar tissue, clinically manifesting as a loss of elasticity, tissue thickening, and organ-specific functional consequences. In addition to improving the existing technologies and guidelines directing the administration of radiotherapy, understanding the pathogenesis underlying radiation fibrosis is essential for the success of cancer treatments. This review integrates the principles for radiotherapy dosimetry to minimize off-target effects, the tissue-specific clinical manifestations, the key cellular and molecular drivers of radiation fibrosis, and emerging therapeutic opportunities for both prevention and treatment.

Keywords: Dosimetry constraints; Experimental therapeutics; Extracellular matrix; Radiation fibrosis; Radiotherapy.

Publication types

Review