New Exploration of Therapeutic Targets for Radiation Pneumonitis: Comparative Analysis of Molecular Pathways in Radiation-Induced and LPS-Induced Pneumonitis.

Radiation pneumonitis (RP) is a common complication of radiotherapy that significantly limits the tolerable radiation dose, thereby compromising treatment outcomes. In severe cases, it can become life-threatening. Currently, the management of RP relies primarily on glucocorticoids. However, this approach is associated with several drawbacks, including markedly increased risks of immunosuppression and infection, metabolic disturbances, musculoskeletal injury, gastrointestinal adverse effects, and most importantly- a potential compromise of antitumor efficacy. Moreover, current treatments for RP and radiation induced pulmonary fibrosis remain unsatisfactory, underscoring the need for mechanistic studies and the exploration of novel therapeutic targets and strategies. RP and lipopolysaccharide (LPS) -induced pneumonitis, originating from Gram-negative bacteria, represent two distinct forms of pulmonary inflammation. We compare their molecular mechanisms-with both shared pathways and key distinctions despite clinical similarities-and explore diverse therapies, including anti-inflammatory responses, antioxidant defenses, gut microbiota regulation, cell death modulation, mitophagy enhancement, among others. In particular, we highlight therapies and targets that have shown efficacy in LPS-induced pneumonitis but have not yet been investigated in the context of RP. These insights may offer valuable guidance for both clinical management and fundamental research on RP.