Tumor cell DNA damage by ionizing radiation

The phrase “tumor cell DNA damage by ionizing radiation” refers to the induction of DNA lesions—most notably, DNA double-strand breaks (DSBs), single-strand breaks (SSBs), base damage, and DNA–protein crosslinks—within tumor cells, as a consequence of exposure to ionizing radiation.[2][3][7][9] Ionizing radiation inflicts DNA damage through both direct energy deposition onto DNA and indirect mechanisms involving the generation of reactive oxygen species (ROS) that attack DNA.[2][3][7] The generation of DSBs is the primary cytotoxic lesion leading to tumor cell death and underpins the effectiveness of radiotherapy in cancer treatment.[9][10] Tumor cell radiosensitivity or resistance is largely determined by the intrinsic ability of the cancer cells to recognize and repair radiation-induced DNA damage via pathways such as homologous recombination and non-homologous end joining.[3][5][9] DNA damage signaling also triggers cell cycle arrest and can engage programmed cell death (apoptosis) if the damage is too extensive to be repaired.[9][4] Modulating DNA damage and repair machinery, often with radiosensitizers such as PARP or DNA-PK inhibitors, can enhance the efficacy of ionizing radiation in killing tumor cells, but also carries safety risks, notably to healthy tissue.[9][10] This biological process is targeted therapeutically but is not itself a defined molecular entity or druggable receptor.

Induce DNA double-strand breaks (DSBs) and other DNA lesions[2][3][7][9] Inhibit repair of DNA damage to enhance radiosensitivity (e.g., PARP inhibition, DNA-PK inhibition)[10] Promote mitophagy to sensitize tumor cells to radiation[1]