Background: Inflammation is the response of the immune system that guards the body
against several harmful stimuli in normal conditions. However, in response to ionizing radiation that
leads to a massive cell death and DNA aberrations, this phenomenon causes various side effects in
normal tissues. Inflammation is involved in various side effects such as gastrointestinal toxicity, mucositis,
skin reactions, nervous system damage, pneumonitis, fibrosis and so on.
Discussion: Observations have proposed that inflammatory mediators are involved in the toxic effect of ionizing
radiation on non-irradiated cells via a phenomenon named bystander effect. Inflammation in both irradiated
and non-irradiated cells can trigger genomic instability, leading to increased risk of carcinogenesis.
Targeting the inflammatory mediators has been an interesting idea for improving the therapeutic ratio
throughout the reduction of normal tissue injury as well as an increase in tumor response to radiotherapy.
Conclusion: So far, various targets have been proposed for the amelioration of radiation toxicity in
radiotherapy. Of different targets, NF-κB, COX-2, some of NADPH Oxidase subfamilies, TGF-β, p38
and the renin-angiotensin system have shown promising results. Interestingly, inhibition of these targets
can help sensitize the tumor cells to the radiation treatment with some mechanisms such as suppression
of angiogenesis and tumor growth as well as induction of apoptosis. In this review, we focus
on recent advances on promising studies for targeting the inflammatory mediators in radiotherapy.