Radiation therapy is a cornerstone of cancer treatment, targeting tumor cells through DNA damage and subsequent induction of various forms of cell death. This chapter explores the multifaceted biological effects of Radiation therapy (RT), highlighting its ability to trigger different lethal and non-lethal death mechanisms. The mechanisms underlying these responses involve complex interactions between radiation-induced DNA damage, reactive oxygen species production, and disruption of cellular homeostasis. RT therapeutic efficacy is influenced by factors such as tumor type, microenvironment, and the balance between cell death and survival pathways. Advances in understanding how RT impacts cell death mechanisms, including the modulation of ferroptosis and pyroptosis, have unveiled new opportunities to enhance radiosensitivity and overcome tumor resistance. Furthermore, non-lethal processes, such as senescence and mitotic catastrophe, underscore the potential of RT to suppress tumor progression through mechanisms beyond direct cytotoxicity. This chapter emphasizes the need for integrating molecular insights with clinical applications to optimize the efficacy of RT while minimizing damage to healthy tissues. By examining emerging strategies, such as the exploitation of immune responses and targeting tumor microenvironmental factors, this work provides a comprehensive foundation for advancing radiotherapy in oncology.
