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Radiation-induced lung injury is a common side effect of therapeutic irradiation for thoracic cancers. Patients with radiation-induced lung damage have distinct changes in lung metabolism associated with the incidence of fibrosis. A study analyzed the exhaled breath condensate of subjects with CT-confirmed lung lesions after TR for lung cancer and compared it to healthy subjects, smokers, and cancer patients who had not yet received TR. The lung metabolomic profile of the fibrosis case group was significantly different from the control groups, with increased levels of lactate and upregulations of the fatty acid oxidation and glutamate pathways. The results suggest that preferential conversion of pyruvate to lactate deprives the tricarboxylic acid cycle of a key input, requiring compensatory upregulation of alternative energy inputs to meet the metabolic demands of chronic wound repair. This approach could inform future mechanistic investigations and development of novel therapeutic targets.
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