Radiotherapy-Induced Skin Injuries (RISIs): Mechanisms and Therapeutic Approaches

Radiotherapy (RT) remains one of the most essential and effective modalities in cancer treatment, administered to more than half of all patients for both curative and palliative purposes. Despite remarkable technological advances in precision targeting and dose modulation, radiation-induced skin injuries (RISIs) remain among the most common and distressing side effects of RT, affecting approximately 85-95% of patients. These cutaneous toxicities—ranging from transient erythema and dry desquamation to severe ulceration, fibrosis, and necrosis—reflect complex cellular and molecular disruptions. The clinical management of RISIs remains inconsistent, with no universally accepted standard of care. While traditional topical agents and dressings provide symptomatic relief, their efficacy is limited by poor stability and insufficient antioxidant activity. Recent evidence underscores the promise of targeted molecular therapies—such as TGF-β/Smad3 and COX-2 inhibition—alongside regenerative approaches involving mesenchymal stem cells, biomaterials, and nanotechnology-based drug delivery systems. Furthermore, integrating predictive biomarkers may enable personalized prevention and treatment strategies. This review synthesizes current insights into the pathophysiological and molecular mechanisms of RISIs, highlighting both established and emerging therapeutic modalities. By bridging mechanistic understanding with translational innovation, it aims to inform the development of more effective, biologically guided interventions that mitigate toxicity, enhance tissue repair, and ultimately improve the quality of life and treatment outcomes for cancer patients.