Mechanisms and therapeutic potential of therapy-induced cellular senescence in radiotherapy- and chemotherapy-related alimentary tract mucositis.

PURPOSE: Radiotherapy- and chemotherapy-related alimentary tract mucositis is a common complication of cancer treatment, yet the role of cellular senescence during these treatments and post-treatment mucosal repair has not been systematically discussed. This narrative review summarizes the potential involvement of therapy-induced cellular senescence (TIS) in cumulative mucosal injury during treatment and in post-treatment healing and remodeling, and discusses the therapeutic potential and limitations of targeting senescence. METHODS: This narrative review synthesizes evidence from studies on TIS, SASP biology, oral and gastrointestinal mucositis, oxidative stress, extracellular matrix remodeling, microbial dysbiosis, mucosal wound repair, and senescence-targeted interventions. RESULTS: TIS may amplify mucosal injury during treatment by sustaining ROS accumulation and oxidative stress, contributing to extracellular matrix remodeling, and promoting dysbiosis-prone mucosal microecological remodeling. During post-treatment healing, transient senescence may support immune recruitment, debris clearance, and repair initiation, whereas persistent senescence may maintain inflammatory SASP signaling, impair epithelial regeneration, and promote abnormal tissue remodeling. These processes may operate in both oral and gastrointestinal mucositis, but their dominant cellular sources, microbial interfaces, and repair programs are likely organ-specific. Current experimental evidence also suggests that senescence-targeted strategies may attenuate mucosal injury, although their timing and safety remain critical issues. CONCLUSION: TIS may contribute to both the cumulative injury phase during treatment and the healing and remodeling phase after treatment in alimentary tract mucositis. Senescence-targeted strategies have therapeutic potential, but their translation requires careful consideration of intervention timing, local delivery, tumor safety, and preservation of early repair-promoting senescence.