Core Viewpoint - The study reveals that radiotherapy induces the secretion of spermidine synthase from tumor cells, leading to skeletal muscle weakness due to changes in polyamine metabolism and collagen accumulation in muscle tissue [2][4][6]. Group 1: Mechanism of Action - Radiotherapy stress activates the metabolism of phospholipids in tumor cell membranes, resulting in increased levels of free arachidonic acid (ArA), which enhances the ISGylation of spermidine synthase (SRM) [4][5]. - The accumulation of ArA promotes the packaging of SRM into small extracellular vesicles (sEV), which are then absorbed by skeletal muscle, leading to muscle weakness [4][6]. Group 2: Clinical Implications - The study suggests that the antihypertensive drug Losartan can effectively inhibit the ISGylation of SRM, blocking its secretion and significantly improving pathological changes in skeletal muscle post-radiotherapy [5][7]. - This provides a theoretical basis and potential intervention target for developing new radioprotective agents to alleviate the side effects of radiotherapy [5][7].