Abstract
It is well-known that Radiation-induced fibrosis (RIF) is a late event occurring months to years after the initial radiation exposure. Fibrotic lesions have been shown to manifest in many tissues including the skin, heart, lung, liver and kidney. Fibrosis occurs due to abnormal accumulation of extracellular matrix (ECM) proteins that result in loss of normal tissue and organ function. The cell type involved in RIF is myofibroblasts, which do not undergo apoptosis after healing but instead continue to accumulate, producing excessive amounts of ECM proteins, thereby damaging the tissues and organs. Reactive oxygen species, generated in response to radiation, is one signal that helps maintain the myofibroblast phenotype. In this review, we discuss molecular mechanisms leading to this late radiation event, known biomarkers for prediction, preclinical animal models of radiation-induced toxicity and current clinical trials designed for mitigation and treatment of radiation-induced fibrosis. We also discuss other physical properties such as linear energy transfer (LET) than the ones used in the clinics today which may have the potential to change our understanding on this inevitable pathway from radiation treatment to organ fibrosis.
Highlights
Radiation-induced Fibrosis (RIF) develops several months or years following radiotherapy [1,2,3]
We summarize and discuss this pathway from initial radiotherapy to the tissue fibrotic endpoint with an aim to shed light into the importance of careful planning and evaluation on an individualized basis in order to reduce unwanted complications of radiation with severe consequences
Since the TGF-β/Smad pathway is a major player in the development of fibrosis, its inhibition has been implicated as a possible therapeutic intervention
Summary
Radiation-induced Fibrosis (RIF) develops several months or years following radiotherapy [1,2,3]. Ionizing radiation sources used in cancer therapy include gamma rays and X-rays, which possess sufficient energy to displace electrons from atoms When these energy waves interact with water molecules, it leads to excitation and ionization of water molecules to form free radicals and ROS. Maintenance of homeostasis is achieved by biochemical mechanisms in place in the normal physiological setting, to counteract the damaging effects of free radical damage by ROS These include action of enzymes such as super oxide dismutase (SOD) and DNA methyltransferases, p53 interplay and its regulation to restore the cell to its normal redox state. Increased production of ROS lead to toxicity of cells of parenchymal origin, which initiate a cascade, altering the mileu of cytokines in the microenvironment, leading to peroxidation of lipids, oxidation of DNA and protein and activation of proinflammatory cytokines both in vitro and in vivo [43,44,45,46]. A summary of effectors of fibrosis and the biochemical mechanisms involved are illustrated in (Table 1)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
